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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Acute toxicity: oral, rat (male/female) (Guideline studies with various products containing different PAA concentrations):
- LD50: > 2000 mg/kg bw (male/female) (based on product (0.15% / 0.89% peracetic acid))
- LD50: 185 to 3622/kg bw (male/female) (based on product (2.6 - 17% peracetic acid))
- LD50: 50 - 500 mg/kg bw (male/female) (based on product (35% peracetic acid))
Acute toxicity: inhalation, rat (male/female)  (Guideline studies with various products containing different PAA concentrations):
- 4h-LC50: 204 mg/m³ (4080 mg/m³ based on product containing 5% peracetic acid)
-  RD50: 5.4 ppm (17 mg/m³) pure peracetic acid (generated from a mixture of peracetic acid /HP/Acetic acid)
Acute toxicity: dermal (Guideline studies with various products containing different PAA concentrations):
- LD50: > 2000 mg/kg bw (rat, male/female) (based on product <1% peracetic acid)
- LD50: >1147 mg/kg bw (rabbit, male/female) (based on product ≥1% peracetic acid)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Comparable to guideline study with acceptable restrictions (Only 2 dose levels; no LD50 determined; purpose: determination of approximative oral toxicity.)
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Only 2 dose levels were tested. No LD50 was determined
Principles of method if other than guideline:
Preliminary study to determine the approximate oral toxicity of the test material. Only 2 dose levels were tested. No LD50 was determined
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: Tac:N[SD]fBR
- Source: Taconic Farms, Germantown, NY, USA
- Age: Young adult
- Weight at study initiation: 340-360 g (males), 233-262 g (females)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Doses per time period: Single dose
- Application volume: Not stated, calculated to 0.0442 and 0.442 mL/kg bw based on the specific gravity of the test material (1.13 g/mL)
Doses:
50 and 500 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 14 days
- Examinations: mortality, clinical signs, body weights, necropsy
- The animals were observed for mortality and clinical signs at approximately 3 hours after administration on the day of dosing and daily thereafter for 14 days. Body weights were taken on the day of dosing and again on day 7 and 14.
Statistics:
LD50 was not determined.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
50 - 500 mg/kg bw
Remarks on result:
other: based on product (35% PAA) (mortality: 10/10 at 500 mg/kg bw; 1/10 at 50 mg/kg bw)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
17.5 - 175 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
All rats receiving 500 mg/kg died withing 3 days of dosing. One male rat receiving 50.0 mg/kg died on day 13.
Clinical signs:
other: Dyspnea, oral discharge, chromorhinorrhea, decreased locomotion
Gross pathology:
Surviving animals had no gross lesions. Gross lesions among decedents included blood filled stomachs and intestines, consolidated lung (1 rat), white livers, spleens, kidneys and stomachs.
Other findings:
No sex-specific differences were observed.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study, the test material is temporarily approximated to be moderately toxic when orally administered undiluted to Sprague-Dawley rats.
Based on the information provided in this study and taking into account the results reported, the test material containing 35% peracetic acid has to be considered as harmful if swallowed (Xn, R22).
Executive summary:

To determine the approximate and temporary oral toxicity of the test material groups of 5 male and 5 female rats per group were orally dosed with 35 % peracetic acid undiluted at dosage levels of 50 and 500 mg/kg bw. Observations for toxicity were conducted at approximately 3 hours after dosing and daily thereafter for 14 days. Body weights were recorded on days 0, 7 and 14 of the study. A gross necropsy was performed on all animals.

All rats of the high dose group died within 3 days. One male rat of the low dose died on day 13. The predominant clinical signs observed were dyspnea, oral discharge, chromorhinorrhea, decreased locomotion. All survivors gained weight during the study. Internal gross necropsy findings among decedents included blood filled stomachs and intestines, livers, spleens, kidneys and stomachs which appeared white on the surface, and a consolidated lung in one rat. Animals which were sacrificed on day 14 appeared normal at necropsy.

No LD50 value was determined. Based on the mortality rates, the LD50 is between 50 - 500 mg/kg bw corresponding to 17.5 - 175 mg peracetic acid/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Germantown, NY, USA
- Age at study initiation: Young adult
- Weight at study initiation: 233-262 g (males), 209-239 g (females)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Application volume: 1.2-1.3 mL (males); 1.0-1.2 mL (females)
- Doses per time period: Single dose
- Volume administered or concentration: The test material, as a 0.15 % use dilution in deionized water, was introduced directly into the stomach of each animal by means of a ball-tipped intubation needle.
Doses:
5000 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 14 days
- Examinations: The animals were observed for mortality and clinical signs at 0.5, 1, 2, 3, 4 and 6 hours on the day of dosing and twice daily thereafter for 13 day; on day 14 were observed once. Body weights were taken on the day of dosing and again on days 7 and 14. After the study the animals were submitted to gross necropsy.
Statistics:
Not applicable, only one dose (limit test)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: based on product (0.15% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7.5 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
There were no deaths.
Clinical signs:
other: All rats remained healthy during the study and all rats gained weight by day 14 of the study.
Gross pathology:
There were no gross internal lesions observed in any animal at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was considered to be practically non-toxic; LD50 greater than 5000 mg/kg bw corresponding to greater than 7.5 mg peracetic acid/kg bw (no lethal effect at maximal dose)
Executive summary:

In an acute oral toxicity study 10 rats (5 males and 5 females) were dosed with a peracetic acid solution (0.15 %) at a dose level of 5000 mg/kg bw. Observations for clinical signs and toxicity were made after 0.5, 1, 2, 3, 4 and 6 hours and twice daily until sacrifice on day 14. Body weights were recorded on days 0, 7 and 14. A gross necropsy was performed on all animals. There were no mortalities or clinical signs. All rats remained healthy and gained weight during the study. At necropsy, no gross lesions were observed. Hence, the LD50 is greater than 5000 mg/kg bw corresponding to greater than 7.5 mg peracetic acid/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: Albino HSD:SD
- Source: Harlan Sprague Dawley Inc. Indianapolis, US
- Age: Young adult
- Weight at study initiation: 231-306 g (males), 162-219 g (females)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Doses per time period: Single dose
- Application volume: 0.0433, 0.216, 0.433, 0.866, 4.37 mL/kg
Doses:
50, 250 (additional levels for females), 500, 1000 and 5050 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Number of animals per group: 5 per sex (only females in the two lowest dose groups)
- Post-exposure period: 14 days
- Observations for mortality and clinical/behavioral signs of toxicity were made at least three times on the day of dosing and at least once daily thereafter for 14 days. All animals were subjected to gross necropsy and all abnormalities were recorded.
Statistics:
The LD50 value was calculated by a computer program utilizing probit analysis.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
652 mg/kg bw
Remarks on result:
other: based on product (11.7% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
846 mg/kg bw
Remarks on result:
other: based on product (11.7% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
314 mg/kg bw
Remarks on result:
other: based on product (11.7% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
76.2 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
98.9 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
36.7 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
0, 4, 5 male rats died in the 500, 1000, 5050 mg/kg bw groups, respectively.
0, 3, 3, 4, 5 female rats died in the 50, 250, 500, 1000, 5050 mg/kg bw groups, respectively.
Clinical signs:
other: Activity decrease, crust around nose and eyes, diarrhoea, gasping, nasal and ocular discharge, piloerection, polyuria, ptosis, staining of muzzle and back, salivation, respiratory chirp, emaciation and laboured breathing
Gross pathology:
No abnormalities in animals that survived until scheduled termination of the study. Animals that died during the observation period showed stained and matted muzzle and anal areas, discoloured tongue, gas in the GIT, discoloured stomach, lungs, liver, spleen and contents of the GIT.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 values for acute oral toxicity of Proxitane WW12 were determined to 652 mg/kg bw (overall) and 846 mg/kg bw for males, 314 mg/kg bw for females corresponding to 76.2 mg peracetic acid/kg bw (combined), 98.9 mg peracetic acid/kg bw (males) and 36.7 mg peracetic acid/kg bw (females). The formulation has to be considered as harmful if swallowed (Xn, R22).
95 % confidence limits:
Male 846 mg/kg: 662 - 1082 mg/kg
Female 314 mg/kg: 120 - 819 mg/kg
Combined 652 mg/kg: 477 - 893 mg/kg
Executive summary:

The test substance, Proxitane WW12, was evaluated for its acute oral toxicity potential in albino rats when administered as gavage doses at levels of 500, 1000 and 5050 mg/kg bw to males and females, and additional levels of 50 and 250 mg/kg bw to females. Observations for clinical signs and toxicity were made three times on the day of dosing and then once daily until sacrifice on day 14. Body weights were recorded on days 0, 7 and 14 or at time of discovery after death. A gross necropsy was performed on all animals.

Mortalities occurred in all dose groups except the lowest. i.e. 50 mg/kg bw for females and 500 mg/kg bw for males. In the highest dose groups (5050 mg/kg bw) all animals died. Clinical signs included activity decrease, crust around nose and eyes, diarrhoea, gasping, nasal and ocular discharge, piloerection, polyuria, ptosis, staining of muzzle and back, salivation and respiratory chirp. These signs had subsided by the end of the 14 days observation period in all surviving animals. Animals that died during the course of the study also showed signs of emaciation and laboured breathing.

The LD50 values for acute oral toxicity of Proxitane WW12 were determined to 652 mg/kg bw (overall) and 846 mg/kg bw for males, 314 mg/kg bw for females corresponding to 76.2 mg peracetic acid/kg bw (combined), 98.9 mg peracetic acid/kg bw (males) and 36.7 mg peracetic acid/kg bw (females).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: Albino HSD:SD
- Source: Harlan Sprague Dawley Inc. Indianapolis, US
- Age: Young adult
- Weight at study initiation: 228-308 g (males), 151-203 g (females)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Doses per time period: Single dose
- Application volume: 0.044, 0.089, 0.223, 0.445, 0.891, 4.5 mL/kg
Doses:
50 (additional level for females), 100, 250, 500, 1000 and 5050 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 14 days
- Number of animals per group: 5 per sex (only females in the lowest dose group)
- Examinations: Mortality, clinical/behavioural signs, body weights, necropsy
- Timepoints for observations: Mortality and clinical/behavioral signs of toxicity were made at least three times on the day of dosing and at least once daily thereafter for 14 days.
Statistics:
The LD50 value was calculated by a computer program utilizing probit analysis.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
185 mg/kg bw
Remarks on result:
other: based on product (4.89% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
316 mg/kg bw
Remarks on result:
other: based on product (4.89% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
118 mg/kg bw
Remarks on result:
other: based on product (4.89% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
9 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
15.5 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
5.8 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
1, 3, 3, 3, 5 male rats died in the 100, 250, 500, 1000, 5050 mg/kg bw groups, respectively.
0, 4, 5, 3, 3, 5 female rats died in the 50, 100, 250, 500, 1000, 5050 mg/kg bw groups, respectively.
Clinical signs:
other: Piloerection, salivation, activity decrease, nasal and ocular discharge, diarrhoea, polyuria, gasping, staining of the muzzle, respiratory gurgle and chirp, ptosis, crust around the nose and in animals that died during study: sensitivity to touch, dark ur
Gross pathology:
No abnormalities in surviving animals. Findings in animals that died include discolouration of the tongue, liver, stomach, small intestine, lungs and contents of the GIT, ocular discharge, gas in GIT, stained muzzle, anal and urogenital hair, matted hair around eyes and muzzle.
Other findings:
The results show that no appropriate dose response relationship was found. Furthermore females seem to be more sensitive than males.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LD50 values for acute oral toxicity of Proxitane AHC were determined to 185 mg/kg bw (overall) and 316 mg/kg bw for males, 118 mg/kg bw for females corresponding to 9.0 mg peracetic acid/kg bw (combined), 15.5 mg peracetic acid/kg bw (males) and 5.8 mg peracetic acid/kg bw (females). Based on the acute oral toxicity determined, the formulation has to be considered as harmful.
Executive summary:

The test substance, Proxitane AHC, was evaluated for its acute oral toxicity potential in albino rats when administered as gavage doses at levels of 100, 250, 500, 1000 and 5050 mg/kg bw to males and females, and an additional level of 50 mg/kg bw to females. Observations for clinical signs and toxicity were made three times on the day of dosing and then once daily until sacrifice on day 14. Body weights were recorded on days 0, 7 and 14 or at time of discovery after death. A gross necropsy was performed on all animals.

No mortalities occurred in the 50 mg/kg bw dose group. Clinical signs of toxicity included discolouration of the tongue, liver, stomach, small intestine, lungs and contents of the GIT, ocular discharge, gas in GIT, stained muzzle, anal and urogenital hair, matted hair around eyes and muzzle. Animals surviving the 14-day observation period were asymptomatic at termination of the study apart from piloerection, body weight gain in these animals was mostly unaffected. Abnormal necropsy findings occurred only in the animals that died during the test and pertained primarily to the contents of the GIT and discolouration of the liver, stomach, small intestine, tongue and lung.

The LD50 values for acute oral toxicity of Proxitane AHC were determined to 185 mg/kg bw (overall) and 316 mg/kg bw for males, 118 mg/kg bw for females corresponding to 9.0, 15.5 and 5.8 mg peracetic acid/kg bw, respectively. There was no appropriate dose response relationship. Furthermore females seem to be more sensitive than males.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
GLP compliance:
yes
Remarks:
(Quality assurance statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: HC/CFY Remote
- Source: Hacking and Churchill Ltd. Huntingdon, UK
- Age: 4-6 weeks
- Weight at study initiation: 97-136 g
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Doses per time period: Single dose
- Concentration in vehicle: 12.6, 20.0, 32.0, 50.0 % (w/v)
- Application volume: 10 mL/kg bw
Doses:
1260, 2000, 3200 and 5000 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- post-exposure period: 14 days
- Examinations: Mortality, toxic signs, bodyweights, necropsy
- The animals were observed for gross signs of systemic toxicity and mortality several times during the day of dosing and at least twice daily thereafter for a total of 14 days. All animals were subjected to a gross necropsy.
Statistics:
Method of determination of LD50: Probit.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
Remarks on result:
other: based on product (4.5% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 900 mg/kg bw
Remarks on result:
other: based on product (4.5% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Remarks on result:
other: based on product (4.5% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
77 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
86 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
63 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
1, 2, 5, 5 male rats died in the 1260, 2000, 3200, 5000 mg/kg bw groups, respectively.
1, 5, 5, 5 female rats died in the 1260, 2000, 3200, 5000 mg/kg bw groups, respectively.
Clinical signs:
other: Piloerection, hunched posture, abnormal gait (waddling), lethargy, pallor of extremities in all rats. In some rats the following signs were observed: decreased respiratory rate, ptosis, increased salivation, rales, abdominal distension, comatose-like cond
Gross pathology:
Distension and congestion of the stomach wall with thickening of the pyloric sphincter, congestion of duodenum, possibly ulcerated area in stomach.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 of 5 % peroxyacetic acid was estimated to be 1700 mg/kg bw (combined), 1900 mg/kg bw for males and 1400 mg/kg bw for females, corresponding to 77, 86 and 63 mg peracetic acid/kg bw, respectively. Thus, the formulation containing 4.5% peroxyacetic acid has to be considered as harmful if swallowed (Xn, R22).
Executive summary:

In an acute toxicity test with peroxyacetic acid 5 %, groups of 5 male and 5 female rats received oral doses by gavage of 1260, 2000, 3200, 5000 mg/kg bw, applied as diluted watery solution with a total volume of 10 ml/kg bw. Observations for clinical signs were performed soon after dosing and at frequent intervals for the remainder of day 1. On subsequent 13 days the animals were observed at least twice per day. The time of death, the nature, severity, approximate time of onset and duration of toxic signs were recorded. Individual body weights were recorded on day 1, 8 and 15 and at death. A gross necropsy was performed in all animals.

Mortalities occurred in all dose groups within 8 days after dosing. Animals of the highest dose group died within 24 hours. Signs of reaction to the treatment observed in all rats were piloerection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, and pallor of the extremities. Predominantly in higher dose groups the following signs were observed: decreased respiratory rate, ptosis, increased salivation, rales, abdominal distension, comatose-like condition, gasping, increased lacrimation.

The LD50 of 5 % peroxyacetic acid was estimated to be 1700 mg/kg bw (combined), 1900 mg/kg bw for males and 1400 mg/kg bw for females, corresponding to 77, 86 and 63 mg peracetic acid/kg bw, respectively.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: Hsd: Sprague-Dawley SD
- Source: Harlan Nossan, Correzzana, Italy
- Age: 5-6 weeks
- Weight at study initiation: 187-207 g (males), 153-176 (females)
Route of administration:
oral: gavage
Vehicle:
other: Alembicol D (fractionated coconut oil)
Details on oral exposure:
- Doses per time period: Single dose
- Volume administered or concentration: the appropriate dose volume, calculated for each animal was administered by gavage at a dose volume of 10 mL/kg using a rubber catheter attached to a syringe
- Application volume: 10 mL/kg
Doses:
1200, 1680, 2352 and 3293 mg/kg bw (of the product)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- post-exposure period: 14 days
- Animals were observed for clinical signs immediately upon dosing, approximately 1, 2 and 4 hours after dosing and daily thereafter for a total of 14 days. After the study the animals were submitted to gross necropsy.
Statistics:
The mortality data from all groups were analysed using the methods of Finney. Method of determination of LD50: Probit.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 622 mg/kg bw
Remarks on result:
other: based on product (5.6% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
3 271 mg/kg bw
Remarks on result:
other: based on product (5.6% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
4 217 mg/kg bw
Remarks on result:
other: based on product (5.6% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
202.8 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
183.2 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
236.2 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
0, 0, 2, 2 male rats died in the 1200, 1680, 2352, 3293 mg/kg bw groups, respectively.
0, 0, 2, 1 female rats died in the 1200, 1680, 2352, 3293 mg/kg bw groups, respectively.
Clinical signs:
other: Commonly: soft/mucoid faeces, reduced activity, piloerection Sporadic: moribund appearance, hunched posture, swollen abdomen, prolapsed penis, part-closed eyes, pallor
Gross pathology:
Surviving animals showed no abnormalities. Animals that died during the study showed significant abnormalities in liver (either dark or pale spots), stomach (thickened and white) and the GIT (dark red and containing dark red material).
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test substance was determined to 3271 mg/kg bw in males and 4217 mg/kg bw in females, giving an overall LD50 of 3622 mg/kg bw corresponding to 183.2 mg peracetic acid/kg bw (males), 236.2 mg peracetic acid/kg bw (females) and 202.8 mg peracetic acid/kg bw (combined). The test material has not to be classified with respect to acute oral toxicity.

Executive summary:

The acute toxicity of Oxystrong 5 was investigated following administration of a single oral dose to groups of male and female rats. Dose levels were set following a preliminary study to 1200, 1680, 2352 and 3293 mg/kg bw. Animals were observed for a 14 day period after which surviving animals were killed and subjected to necropsy examination.

Mortalities occurred at the 2 highest dose levels investigated. Soft or mucoid faeces, reduced activity and piloerection were commonly observed following dosing at all dose levels investigated. Individual animals dosed with 2352 mg/kg bw appeared moribund prior to death. One animal dosed with 3293 mg/kg bw exhibited hunched posture, swollen abdomen, prolapsed penis, part-closed eyes and pallor before death on day 8. Surviving animals had generally recovered within 3 days of dosing. Changes in body weight of the surviving animals were generally not remarkable. Surviving animals showed no abnormalities. Necropsy examination of the descendent animals revealed significant abnormalities in the liver, stomach and regions of the GIT.

The LD50 of the test substance was determined to 3271 mg/kg bw in males and 4217 mg/kg bw in females, giving an overall LD50 of 3622 mg/kg bw corresponding to 183.2, 236.2 and 202.8 mg peracetic acid/kg bw, respectively.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Harlan Sprague Dawley, Inc., Indianapolis, Indiana, USA
- Age: Young adult
- Weight at study initiation: 200-330 g
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Doses per time period: Single dose
- Concentration in vehicle: 1.52 % peracetic acid
- Volume administered or concentration: The test material was initially administered as a 25 % w/v formulation in distilled water at a dose level of 2500 mg/kg. Due to the resulting mortality and necropsy findings, additional dose levels of 2500, 1880 and 1250 mg/kg were conducted using a 10 % w/v formulation in water. Only data derived using the constant test material concentration of 10% was used for the LD50 calculation.
Doses:
1250, 1880 and 2500 mg/kg bw of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 14 days
- Examinations: Mortality, clinical symptoms, bodyweights, necropsy
- The animals were observed for gross signs of systemic toxicity and mortality several times during the day of dosing and at least twice daily thereafter for a total of 14 days. All animals were subjected to a gross necropsy.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 780 mg/kg bw
Remarks on result:
other: based on product (15.2% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
271 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
No deaths in the lowest dose. 7/10 and 10/10 died in the 1880 and 2500 mg/kg bw dose groups, respectively.
Clinical signs:
other: Clinical signs observed in many of the animals included slight to severe depression, saliva stains, piloerection, respiratory distress, bloating of the abdominal region and emaciation.
Gross pathology:
Congested kidney, enlarged stomach with semi-liquid food-like content. In animals that died during study general observations of irritation or corrosion.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the mortality observed the acute oral LD50 value was calculated to be 1780 mg product/kg bw corresponding to 271 mg peracetic acid/kg bw (male/female). Hence, the test substance has to be considered as harmful if swallowed (Xn, R22).
Executive summary:

The acute oral toxicity of Oxy-15 in rats was evaluated in a study applying groups of 5 male and 5 female Sprague Dawley rats. The test material was initially administered as 25 % w/v formulation in distilled water but was then changed to a 10 % w/v formulation in order to avoid explicit corrosivity. Dose levels then were 1250, 1880, and 2500 mg/kg bw. Only the results from the 10 % formulation experiments were used for the deduction of the LD50.

Mortalities, clinical signs and body weights were recorded for 14 days. A gross necropsy was performed in all animals. Treatment related signs were noted at all dose levels tested. In animals that died during the study, gross necropsy findings included signs typically found in agonal animals and signs seen in response to the oral administration of a severely irritating or corrosive material. Necropsy findings noted in animals that survived the study included right kidney congested in one animal and stomach enlarged containing a large amount of semi-liquid, food-like substance in one animal.

Based on the mortality observed the acute oral LD50 value was calculated to be 1780 mg product/kg bw corresponding to 271 mg peracetic acid/kg bw. (male/female).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Comparable to guideline study. Restrictions: no GLP, limited reporting of results data
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Comparable to guideline study. Restrictions: No GLP, limited reporting of results data (Body weights not recorded)
Principles of method if other than guideline:
Comparable to guideline study. Restrictions: No GLP, limited reporting of results data (Body weights not recorded)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: Bor:WISW
- Source: Winkelmann, Borchen, Germany
- Age: 49-52 days (males), 63-72 days (females)
- Weight at study initiation: 129-168 g (males), 127-141 g (females)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Doses per time period: Single dose
- Application volume: 2.15 mL/kg bw
- Concentration in vehicle: Because application of the volume of 2.15 mL/kg bw of undiluted 15% PAA proved 100% lethal, the test material was diluted down by factors of 4.64, 3.16, 2.15 and 1.47, respectively, achieving the doses specified below.
Doses:
532, 781, 1146 and 1682 (additional level for females) mg/kg bw of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- post-exposure period: 14 days
- The rats were observed at 0.5, 1, 2, 4, 8 and 24 hours after dosing and thereafter once daily until the end of the study.
- Examinations: mortality, clinical signs, necropsy
Statistics:
LD50 was calculated with probit analysis.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 026 mg/kg bw
Remarks on result:
other: based on product (15% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 015 mg/kg bw
Remarks on result:
other: based on product (15% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
153.9 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
152.3 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
0, 1, 4 male rats died in the 532, 781, 1146 mg/kg bw groups, respectively.
0, 1, 3, 5 female rats died in the 532, 781, 1146, 1682 mg/kg bw groups, respectively.
Clinical signs:
other: Piloerection, writhing syndrome, stilted gait, tremor, drawn-in flanks, laboured breathing, irritation of the gastro-intestinal tract Red coloured urine was observed in females of the highest dose group. In the lowest dose group no clinical signs indicat
Gross pathology:
Peritoneal adhesions, discoloured mucosa of the GIT and of the contact area between liver and stomach. In sporadic cases liquid deposits in the abdominal cavity.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 values for acute oral toxicity of peracetic acid 15 % were determined to 1026 mg/kg bw for males and 1015 mg/kg bw for females corresponding to 153.9 mg peracetic acid/kg bw (males) and 152.3 mg peracetic acid/kg bw (females). The formulation has to be considered as harmful if swallowed (Xn, R22).
Executive summary:

Peracetic acid 15 % was administered to rats by gavage at doses of 532, 781, 1146, 1682 mg/kg bw, applied as diluted watery solution with a total volume of 2.15 ml/kg bw. Observations for clinical signs and toxicity were made 0.5, 1, 2, 4, 8 and 24 h after dosing and then once daily until sacrifice on day 14. At study termination a gross necropsy was performed. Mortalities occurred in all dose groups except the lowest. Clinical signs of intoxication included piloerection, writhing syndrome, stilted gait, tremor, drawn-in flanks and laboured breathing. Pathological changes observed in necropsy included peritoneal adhesions, discoloured mucosa of the GIT and of the contact area between liver and stomach. In sporadic cases liquid deposits in the abdominal cavity were found.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: Sprague-Dawley CD
- Source: Charles River Laboratories
- Age: Young adult
- Weight at study initiation: 220-245 g (males), 205-232 g (females)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Doses per time period: Single dose
- Concentration in vehicle: 1.25 % peracetic acid (5 % peracetic acid as a 25 % (w/v) preparation in tap water)
Doses:
1000, 2000 and 4000 mg/kg bw of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 14 days
- Examinations: The animals were observed for mortality and clinical signs at 0.5, 1, 2, 3, 4 and 6 hours on the day of dosing and daily thereafter for 14 days. Body weights were taken on the day of dosing and again on days 7 and 14. After the study the animals were submitted to gross necropsy.
Statistics:
The LD50 calculations were performed using a modified Logit-Linear Regression Program from Texas Instruments Calculator Products Division.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 922 mg/kg bw
95% CL:
1 342 - 2 501
Remarks on result:
other: based on product (5% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 993 mg/kg bw
95% CL:
938 - 3 045
Remarks on result:
other: based on product (5% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 859 mg/kg bw
95% CL:
1 056 - 2 663
Remarks on result:
other: based on product (5% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
96.1 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
99.7 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
93 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
0, 3, 4 male rats died in the 1000, 2000, 4000 mg product/kg bw groups, respectively.
0, 3, 5 female rats died in the 1000, 2000, 4000 mg product/kg bw groups, respectively.
Clinical signs:
other: Abdominal gripping, abdominal distention, loss of muscle control, squinting eyes, staggered gait, tremors, walking on toes, hypersensitivity to touch, splayed hindlimbs, hypothermia, abdominogenital staining, chromorhinorrhoea, decreased/no faeces, unkemp
Gross pathology:
Blanched stomach and intestines, mottled blanched livers, distended stomach with thin linings, darkened red adrenals, white trachea, blood in stomach and intestines.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study, the LD50 of the test material is 1993 mg/kg in male rats, 1859 mg/kg bw in female rats and 1992 mg/kg bw in combined sexes.
Based on the results obtained, the test material has to be considered as harmful if swallowed (Xn, R22).
Executive summary:

Groups of male and female Sprague-Dawley rats were orally administered peracetic acid 5% as a 25% (w/v) preparation in tap water. Observations for toxicity were conducted at approximately 0.5, 1, 2, 3, 4 and 6 hours following dosing and daily thereafter for fourteen days. Body weights were recorded on days 0, 7 and 14 or upon discovery of death. A gross necropsy was performed on all animals.

In the high dose groups 9/10 animals died (4 males and 5 females), in the mid dose groups 6/10 animals died (3 males and 3 females). No mortalities occurred in the low dose group. The most significant clinical signs observed were abdominal gripping, abdominal distention, loss of muscle control, squinting eyes, staggered gait, tremors, walking on toes, hypersensitivity to touch, splayed hindlimbs and hypothermia. Other clinical signs noted included abdominogenital staining, chromorhinorrhoea, decreased/no faeces, unkempt appearance, chromodacryorrhoea, dehydration, decreased locomotion, lacrimation, mydriasis, oral discharge, unthriftiness, leaning to one side, recumbency, abnormal posture and diarrhoea. All signs of toxicity subsided by day 13, however recovery was essentially complete on day 7. All surviving animals gained weight by day 14. During necropsy blanched stomach and intestines, mottled blanched livers, distended stomach with thin linings, darkened red adrenals, white trachea and blood in stomach and intestines were noted.

Under the conditions of this study, the LD50 of the test material is 1993 mg/kg bw in male rats, 1859 mg/kg bw in female rats and 1992 mg/kg bw in combined sexes corresponding to 99.7, 93 and 96.1 mg/kg bw based on peracetic acid.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
(cited as Directive 79/831/EEC, annex V, part B)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: OFA (IOPS)
- Source: Iffa Credo, Saint-Germain sur l’Arbresle, France
- Age: 6-7 weeks
- Weight at study initiation: 160-200 g (males), 140-180 g (females)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Doses per time period: Single dose
- Concentration in vehicle: 0, 25.2, 31.8, 35.6, 40.0, 50.4 g/100 mL for the 0, 1260, 1590, 1780, 2000, 2520 mg/kg bw doses, respectively
- Application volume: 5 mL/kg bw
Doses:
0, 1260, 1590, 1780, 2000 and 2520 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
yes
Remarks:
vehicle control
Details on study design:
- Post-exposure period: 14 days
- Examinations: mortality, clinical/behavioural signs, body weights, necropsy
- The animals were observed for mortality and clinical signs within 1, 2 and 4 hours after dosing, and subsequently at least once daily throughout an observation period of 14 days. All animals were subjected to a gross necropsy.
Statistics:
The LD50 was calculated according to the method of Litchfield and Wilcoxon.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 656 mg/kg bw
Remarks on result:
other: based on product (2.6% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
43 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
0, 0, 1, 3, 4, 5 male rats died in the 0, 1260, 1590, 1780, 2000, 2520 ml/kg bw groups, respectively.
0, 1, 2, 3, 4, 5 female rats died in the 0, 1260, 1590, 1780, 2000, 2520 ml/kg bw groups, respectively.
Clinical signs:
other: In the highest concentrations ataxy, piloerection and swollen abdomen were observed.
Gross pathology:
In the three highest concentrations swollen and blood filled stomachs, regression of the thymus and adherence of the liver with the stomach.
Other findings:
The toxicity between the two sexes is comparable.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The combined LD50 in both sexes for the test material was calculated to 1656 mg/kg bw.corresponding to 43 mg peracetic acid/kg bw. The formulation has to be considered as harmful if swallowed.
Executive summary:

In an acute oral toxicity study six groups of 10 rats (5 male and 5 female) received a single dose of the test material. One group received the vehicle water only. After administration the animals were observed 1, 2 and 4 hours after administration on the first day and daily thereafter for 14 days. Body weights were recorded on days –1, 0, 7 and 14. A gross necropsy was performed in all animals.

The toxicity of the test material was comparable in both sexes. Mortalities occurred in all but the control group. Clinical signs included weariness, ataxia, piloerection and swollen abdomen. Gross necropsy revealed increased thymus, dilated and congested stomach, peritoneal adhesions and ascites.

The combined LD50 in both sexes for the test material was calculated to 1656 mg/kg bw.corresponding to 43 mg peracetic acid/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Strain: SPF-derived Hsd/Cpb:WU
- Source: Harlan/CPB, Zeist, The Netherlands
- Age: Young adult
- Weight at study initiation: 166-186 g (males), 147-173 g (females)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Doses per time period: Single dose
- Volume administered and concentration: The test material was administered by a metal stomach cannula to fasted animals at the following dose levels: 514, 1027 and 2054 mg/kg with dose volumes of 0.5, 1.0 and 2.0 mL/kg respectively. Control animals remained untreated.
Doses:
0, 514, 1027 and 2054 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Post dose observation period: 14 days
- Examinations: mortality, clinical signs, body weights, necropsy
- The rats were observed at 0, 0.5, 2 and 5 hours post dosing and thereafter once daily until the end of the study. Body weights were taken on the day of dosing and again on days 2, 7 and 14. After the study the animals were submitted to necropsy which included inspection of the external appearance, the cervical area, the thoracic and abdominal cavities. Special attention was paid to the stomach.
Statistics:
Method of determination of LD50: Weil.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: based on product (0.89% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: based on product (0.89% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 663 mg/kg bw
95% CL:
1 072 - 2 570
Remarks on result:
other: based on product (0.89% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 17.8 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 17.8 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
14.8 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
One male rat dosed at 514 mg/kg, one female rat dosed at 1027 mg/kg and three female rats dosed at 2054 mg/kg were killed in extremis within 5 days after dosing.
Clinical signs:
other: Abnormal posture, gait (hunched), decreased locomotor activity, sniffing breathing, respiratory difficulties, decreased respiratory rate, vocalization upon handling, ptosis, extended abdomen, stained mouth/nose, nasal discharge.
Gross pathology:
Findings: red spots on lung lobes, maculate thymus, moist skin around mouth, slightly dilated uterus, severe inflammatory changes in GIT (sometimes accompanied by adhesive fibrino purulent peritonitis).
Proxitane 0103 does not show severe gross pathological changes in surviving rats dosed at 514 and 1027 mg/kg. Administration at 2054 mg/kg in females resulted in severe inflammatory changes in the gastro-intestinal tract, indicative of irritation. In male rats no pathological changes were observed at 1027 and 2054 mg/kg.
Other findings:
One male of the low dose group, one female of the mid dose group and three females of the high dose group were killed in extremis.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study the test material has an LD50 > 2000 mg/kg bw (combined). No classification with respect to acute oral toxicity is required based on the combined acute oral LD50 determined.
Executive summary:

In an acute oral toxicity study 40 rats (20 males and 20 females) were dosed with a peracetic acid solution (0.89 %) at a dose levels of 0, 514, 1027 and 2054 mg/kg bw. Observations for clinical signs and toxicity were made after 0, 0.5, 2 and 5 hours and once daily until sacrifice on day 14. Body weights were recorded on days –1, 0, 2, 7 and 14. A gross necropsy was performed on all animals.

Within 5 days after dosing 1 male in the low dose group, 1 female in the mid dose group and 3 females in the high dose group were killed in extremis. Clinical signs in survivors and killed animals included abnormal posture, gait (hunched), decreased locomotor activity, sniffing breathing, respiratory difficulties, decreased respiratory rate, vocalization upon handling, ptosis, extended abdomen, stained mouth/nose, nasal discharge. Signs in survivors were generally slight in severity, recovery was usually complete within 2 days after dosing. Females of the highest dose did not fully recover within the 14 day observation period. Mean body weight and weight gain was slightly reduced in the high dose. In the low and mid dose group as well as in high dosed males no gross pathological changes were observed. High dosed females showed severe inflammations of the GIT.

The LD50 values derived for the product are: > 2000 mg/kg bw (combined), > 2000 mg/kg bw (males), and 1663 mg/kg bw (females) corresponding to > 17.8 mg peracetic acid/kg bw (combined), > 17.8 mg peracetic acid/kg bw (males), and 14.8 mg peracetic acid/kg bw (females), respectively.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Animals of lowest dose group not weighted on day 14
Qualifier:
according to guideline
Guideline:
other: Toxic Substances Control Act (40 CFR)
Principles of method if other than guideline:
Method: other: Toxic Substances Control Act (40 CFR). Methods used are similar to OECD guideline 401.
Deviation: Animals of the lowest dose group were not weighted on day 14.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Harlan Sprague Dawley, Inc.
- Age: young adult
- Weight at study initiation: 215-355 g
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Doses per time period: Single dose by oral gavage
- Concentration in vehicle: 1.53 % peracetic acid
- 25 % w/v formulation in distilled water was applied
Doses:
790, 1250, 1980 and 5000 mg/kg of the product
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 35 days
- Examinations: Mortality, clinical symptoms, bodyweights, necropsy
- The animals were observed for gross signs of systemic toxicity and mortality several times during the day of dosing and at least twice daily thereafter for a total of 14 days. All animals were subjected to a gross necropsy.
Statistics:
Mortality data were evaluated at the end of the observation period by the method of Litchfield and Wilcoxon.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 270 mg/kg bw
Remarks on result:
other: based on product (6.1% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
78 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
0, 2, 2, 5 male rats died in the 790, 1250, 1980, 5000 mg/kg bw groups, respectively.
1, 3, 4, 5 female rats died in the 790, 1250, 1980, 5000 mg/kg bw groups, respectively.
Clinical signs:
other: Gasping, depression, laboured breathing, ataxia, stained fur, emaciation, bloated abdomen, eye squinting, piloerection, red material on muzzle, alopecia, hunched posture
Gross pathology:
Foamy material throughout abdominal cavity, white liver, spleen, stomach, upper intestines, lower intestines haemorrhagic, mottled lungs, stomach bloated with gas, pale and/or congested kidney, stomach adheres to adjacent tissues
Other findings:
The toxicity between the two sexes is comparable.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral LD50 values was estimated to be 1270 mg/kg bw in male and female Sprague-Dawley rats corresponding to 77.6 mg peracetic acid/kg bw. The formulation has to be considered as harmful if swallowed (Xn, R22).
Executive summary:

The acute oral toxicity of Oxonia Active in rats was evaluated in a study applying groups of 5 male and 5 female Sprague Dawley rats. The test material was administered as 25 % w/v formulation in distilled water at dose levels of 790, 1250, 1980 and 5000 mg/kg bw. Dilution was utilised in order to decrease the corrosive effect of the undiluted test material. Mortalities, clinical signs and body weights were recorded for 14 days. A gross necropsy was performed in all animals.

All animals of the highest dose died within 24 hours. 90, 50 and 10 % of the animals died within 13 days in the 1980, 1250 and 790 mg/kg bw dose groups, respectively. Clinical signs included gasping, depression, laboured breathing, ataxia, stained fur, emaciation, bloated abdomen, eye squinting, piloerection, red material on muzzle, alopecia and hunched posture. Gross necropsy showed foamy material throughout the abdominal cavity, white liver, spleen, stomach and upper intestines, haemorrhagic lower intestines, mottled lungs, stomach bloated with gas, pale and/or congested kidney and the stomach adhered to adjacent tissues.

The acute oral LD50 values was estimated to be 1270 mg/kg bw in male and female Sprague-Dawley rats corresponding to 77.6 mg peracetic acid/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Comparable to guideline study with acceptable restrictions (no GLP; limited information on specification of test material)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Comparable to guideline study with acceptable restrictions (no GLP; limited information on specification of test material)
Principles of method if other than guideline:
Comparable to guideline study with acceptable restrictions (no GLP; limited information on specification of test material)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: S.IVANOVAS GmbH & Co, Versuchstierzuchten KG Kisslegg/Allgau, Germany
- Age: 38 days (males), 42 days (females)
- Weight at study initiation: 100-105 g
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
- Application volume: 1.26, 1.59, 2.00, 2.52, 3.18 mL/kg bw
- Doses per time period: Single dose
Doses:
1450, 1830, 2300, 2900 and 3650 mg/kg of the product
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Examinations: mortality, clinical signs, behaviour, food consumption, body weight, necropsy
- Post-exposure period: 4 weeks
Statistics:
LD50 was calculated with the Litchfield and Wilcoxon method.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 540 mg/kg bw
Remarks on result:
other: based on product (10% PAA); calculated from 2.21 ml/kg bw
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 390 mg/kg bw
Remarks on result:
other: based on product (10% PAA); calculated from 2.08 ml/kg bw
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
254 mg/kg bw
Remarks on result:
other: based on PAA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
239 mg/kg bw
Remarks on result:
other: based on PAA
Mortality:
0, 1, 1, 6, 10 male rats died in the 1.26, 1.59, 2.00, 2.52, 3.18 mL/kg bw groups, respectively.
0, 1, 3, 8, 10 female rats died in the 1.26, 1.59, 2.00, 2.52, 3.18 mL/kg bw groups, respectively.
Clinical signs:
other: Sedation, decreased food consumption, decreased body weight gain, ataxia, dyspnea, piloerection, bloody nasal discharge, coma
Gross pathology:
Scarred adhesion of stomach and adjacent tissues, bloody material in GIT, perforation and haemorrhagic erosion of stomach, oesophagus, intra-peritoneal blood deposits
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of PAA 10 % was determined to be 2.21 mL/kg (2540 mg/kg) for males and 2.08 mL/kg (2390 mg/kg) for females.corresponding to 254 mg peracetic acid/kg bw (males) and 239 mg peracetic acid/kg bw (females). The formulation has not to be classified with respect to acute oral toxicity.
Executive summary:

In an acute oral toxicity test groups of 10 male and 10 female Sprague-Dawley rats were exposed to 1.26, 1.59, 2.00, 2.52, 3.18 mL PAA 10%/kg bw. The animals were observed for 4 weeks for clinical signs, change in behaviour, food consumption and body weight. The LD50 was calculated on the basis of the rate of mortality after 14 days. A gross necropsy was performed in all animals either immediately after discovery of death or at the end of the 4 week observation period.


 


Mortalities occurred in all dose groups except the lowest. In the highest dose all animals died within 72 hours. Clinical signs included sedation, decreased food consumption, decreased body weight gain, ataxia, dyspnea, piloerection, bloody nasal discharge and coma. Necropsy revealed incidences of scarred adhesion of the stomach and adjacent tissues, bloody material in the GIT, perforation and haemorrhagic erosion of the stomach and oesophagus and intra-peritoneal blood deposits.


 


The LD50 of PAA 10 % was determined to be 2.21 mL/kg (2540 mg/kg) for males and 2.08 mL/kg (2390 mg/kg) for females.corresponding to 254 mg peracetic acid/kg bw (males) and 239 mg peracetic acid/kg bw (females).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
50 mg/kg bw
Quality of whole database:
Several reliable guideline studies with various dose concentrations of peracetic acid were avaialble.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP Guideline study (particle size not determined, but since a liquid rather than a dust aerosol was generated and in view of the high volatility of PAA, the particles can be considered as respirable.)
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
yes
Remarks:
GLP Guideline study (particle size not determined, but since a liquid rather than a dust aerosol was generated and in view of the high volatility of PAA, the particles can be considered as respirable.)
Principles of method if other than guideline:
GLP Guideline study (particle size not determined, but since a liquid rather than a dust aerosol was generated and in view of the high volatility of PAA, the particles can be considered as respirable.)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Age: Not indicated; Body weight: 192 – 221 g (males), 165 – 195 g (females)
Source: Harlan CPB, Zeist, The Netherlands
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: clean air
Analytical verification of test atmosphere concentrations:
yes
Remarks:
(concentration measurements during each exposure samples of test atmosphere; stability of test atmosphere determined by measuring the opacity)
Duration of exposure:
4 h
Concentrations:
0, 87, 163, 185 and 267 mg peracetic acid/m³ (actual concentration).
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
After the exposure the animals were observed for clinical symptoms and effects on body weight gain. At the end of the 14-day observation period the surviving animals were killed, evaluated for changes of their external appearance and for macroscopical changes in the cervical area and the abdominal and thoracic cavities and for changes in lung weights.

Clinical symptoms (1-4 hours after exposure, daily thereafter), body weights (at allocation to treatment groups, immediately before exposure, on days 2, 7 and 14), gross necropsy and lung weights (at termination)
Statistics:
Body weight and absolute and relative lung weights were evaluated with a one way analysis of variance and subsequently evaluated with the Students' t-test. The LC50 was calculated with logistic regression.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
204 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: based on PAA (5% in product)
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
213 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: based on PAA (5% in product)
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
186 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: based on PAA (5% in product)
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4 080 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: based on product (5% PAA)
Mortality:
Mortalities were observed in the second highest (2 males, 2 females) and highest (4 males, 5 females) dose groups (see Table below). The animals died within 5 days after exposure
Clinical signs:
other: Clinical signs were observed in all treatment groups, however, less severe and frequent in the lowest dose group. These included apathy, respiratory difficulties, reduced respiratory rates, decreased fear reaction, freezing, reduced locomotor activity, tw
Body weight:
The survivors showed a temporary weight loss. Body weights had recovered at the end of the observation period.
Gross pathology:
Absolute lung weights of animals that died in the course of the study were increased when compared to the surviving animals. There were no relevant differences between treated and control animals.
Other findings:
none reported.

MORTALITY:
-----------------------------------------------------------
Exp. Level             Number Dead/Number Treated 
  mg/m³*)          Males       Females       Combined
-----------------------------------------------------------
not exposed         0/5          0/5            0/10
    87              0/5          0/5            0/10
   163              0/5          0/5            0/10
   185              2/5          2/5            4/10
   267              4/5          5/5           10/10
-----------------------------------------------------------*) measured concentrations of peracetic acid


 

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Related to formulation containing 5% peracetic acid
Conclusions:
The LC50 for inhalation of Proxitane AHC is 4080 mg/m³ (combined) corresponding to 204 mg/m³ of peracetic acid, assuming that the test substance contains 5 % of peracetic acid.
Executive summary:

In order to investigate the toxicological effects produced by inhalative exposure to the test material Proxitane AHC, groups of 5 male and 5 female rats were exposed nose-only to measured concentrations of 0, 87, 163, 185 and 267 mg pure peracetic acid/m³ for 4 hours. After the exposure the animals were observed for clinical symptoms and effects on body weight gain. At the end of the 14-day observation period the surviving animals were killed, evaluated for changes of their external appearance and for macroscopical changes in the cervical area and the abdominal and thoracic cavities and for changes in lung weights.

Mortalities were observed in the second highest (2 males, 2 females) and highest (4 males, 5 females) dose groups. The animals died within 5 days after exposure. Macroscopical observations, including increased lung weights were indicative of pulmonary oedema. Clinical symptoms. most likely due to irritating/corrosive action of the test material in the respiratory tract, were observed in all treatment groups. The survivors showed a temporary weight loss. Body weights had recovered at the end of the observation period. No treatment related macroscopical observations and no statistically significant changes of the lung weights were observed in the survivors of all groups at the end of the observation period. In general, no distinction between the effects in males and females could be made. From the observations in this study it is concluded that the effects are caused by the corrosive action of the test material on the respiratory tract of the test animals.

The LC50 for inhalation of Proxitane AHC was 4080 mg/m³ (combined) corresponding to 204 mg/m³ of peracetic acid, assuming that the test substance contains 5 % of peracetic acid. The LC50 for males was 213 and for females 186 mg/m³ of peracetic acid, respectively.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
The study was designed to determine the RD50 (50 % decrease in the respiratory rate) rather than an LC50. However, the RD50 is useful for risk assessment.
Qualifier:
no guideline available
Principles of method if other than guideline:
Investigation of acute sensory irritation after inhalation in mice (RD50 = conc. causing 50% depression in respiratory rate). No guideline available for this study; study investigated endpoints not adopted by official testing guidelines.
GLP compliance:
no
Test type:
other: acute sensory irritation after inhalation
Species:
mouse
Strain:
other: OF1
Sex:
male
Details on test animals or test system and environmental conditions:
- Source: IFFA Credo, Domaine des Oncins, Saint-Germain-sur-l´Abrese, France
- Age: Not stated
- Weight: 20 – 25 g
- No female mice used (not considered to have compromised the study results as no sex differences are assumed as to sensory/local irritation )
Route of administration:
inhalation: vapour
Type of inhalation exposure:
head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Exposures were conducted in a 2.5 L inhalation chamber equipped with four plethysmographs. Mice were restrained in body plethysmographs, while the head was enclosed in the inhalation chamber.
Vapours of acetic acid, hydrogen peroxide, and commercially available peroxyacetic acid were generated by using a peristaltic pump to feed a vaporisation chamber. The pure peroxyacetic acid vapour was generated by buffering the commercial peroxyacetic acid at pH 7 with a phosphate buffer. The different pKa of acetic acid and peroxyacetic acid and the different vapour pressures of peroxyacetic acid and hydrogen peroxide enabled the generation of peroxyacetic acid vapours alone.
Feeding the vaporisation chamber with constantly renewed solutions of buffer and commercially available peroxyacetic acid regulated and ensured the emission of gaseous pure peroxyacetic acid.

A determination of the particle size distribution was not performed.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The respective test atmosphere concentrations on peracetic acid, hydrogen peroxide and acetic acid were analytically verified. For details see chapter Details on study design.
Duration of exposure:
60 min
Concentrations:
Acetic acid: 57, 100, 212 and 389 ppm (140, 247, 523 and 960 mg/m³).
Hydrogen peroxide: 25, 39, 103 and 212 ppm (35, 54, 143 and 295 mg/m³).
Peracetic acid ("pure"): 1.8, 4, 6 and 25 ppm (5.7, 12.6, 18.9 and 78.7 mg/m³).
Peracetic acid ("mixture"): 1.6, 3, 5.6 and 11.6 ppm (5.1, 9.5, 17.7 and 36.6 mg/m³).
No. of animals per sex per dose:
8 per exposure concentration and substance
Control animals:
other: The respiration rate of each mouse before and after exposure was used as a control.
Details on study design:
Exposures were conducted in a 2.5 L inhalation chamber equipped with four plethysmographs. Mice were restrained in body plethysmographs, while the head was enclosed in the inhalation chamber.

Vapours of acetic acid, hydrogen peroxide, and commercially available peroxyacetic acid were generated by using a peristaltic pump to feed a vaporisation chamber. The pure peroxyacetic acid vapour was generated by buffering the commercial peroxyacetic acid at pH 7 with a phosphate buffer. The different pKa of acetic acid and peroxyacetic acid and the different vapour pressures of peroxyacetic acid and hydrogen peroxide enabled the generation of peroxyacetic acid vapours alone.

Feeding the vaporisation chamber with constantly renewed solutions of buffer and commercially available peroxyacetic acid regulated and ensured the emission of gaseous pure peroxyacetic acid.

Breathing frequency and elongation of the period from the end of inspiration until the start of expiration, i.e. the break in respiration, was used as an index of upper respiratory tract irritation.

For the determination of the RD50 values, the maximum decrease in respiratory rate occurring during the exposure period was recorded for each exposure concentration and the RD50 calculated.

As peroxyacetic acid does theoretically not exist alone, a special device composed only of “inert” materials (glass or PVC) was used for the generation of pure peroxyacetic acid from a mixture of peroxyacetic acid, hydrogen peroxide and acetic acid, respectively. Studies performed before with usual aluminium and stainless steel controlled atmosphere devices had demonstrated that 99 % of hydrogen peroxide decomposed before reaching the inhalation chamber. The atmosphere generation device consisted of a motorised syringe (KD Scientific, Bioblock, Illkirch, France) which delivered a constant flow of the product to be generated into a vaporisation chamber composed of column filled with a glass bed. In this vaporisation chamber, a stream of previously heated air flowed counter to the stream of generated product. After being mixed with moistened air, the air directed the generated product towards the inhalation chamber, where a bypass installed at the inlet enabled a constant flow to be maintained inside.

At the beginning of generation, the vaporisation chamber was filled with 7.5 mL of the PAA solution and 7.5 mL of the buffer solution (see also 3.4 above). The chamber was fed by 0.125 mL/min of both PAA and buffer solution, with parallel extraction of 0.25 mL/min of the mixture to keep the level constant. The PAA generated was stripped from the vaporisation chamber by means of a 0.25 L/min flow supplied by a mass flow controller.

A number of examples of the atmospheres generated are given in the table below. Each mean concentration represents five measured values. It should be noted that certain values (or certain limits of the 95 % CI) of the hydrogen peroxide and acetic acid concentrations could be negative. This is due to the method of calculation as the concentration of hydrogen peroxide and acetic acid result from the difference between the total of peroxides and the concentration of peroxyacetic acid, and from the difference between the total of acids and the concentration of peroxyacetic acid. The negative values are explainable by the low atmospheric concentrations of hydrogen peroxide and acetic acid. The results are summarised in the table in section "Any other information on materials and methods incl. tables".
Statistics:
Differences in the respiratory rates before and during exposure to hydrogen peroxide, acetic acid and peroxyacetic acid were analysed statistically by Student´s t-test for paired data. The level of significance was set at P < 0.05. The concentration-response curves were analysed by least-squares linear regression and the RD50 values calculated with their 95 % confidence intervals.
Key result
Dose descriptor:
other: RD50
Effect level:
other: 5.4 ppm = 17 mg/m³ air (analytical)
Exp. duration:
60 min
Remarks on result:
other: based on PAA (pure)
Key result
Dose descriptor:
other: RD50
Effect level:
other: 3.8 ppm = 12 mg/m³ air (analytical)
Exp. duration:
60 min
Remarks on result:
other: based on PAA (36% in mixture with 53%H2O2, 11% acetic acid)
Key result
Dose descriptor:
other: RD50
Effect level:
other: 227 ppm = 560 mg/m³ air (analytical)
Exp. duration:
60 min
Remarks on result:
other: based on acetic acid (pure)
Key result
Dose descriptor:
other: RD50
Effect level:
other: 113 ppm = 157 mg/m³ air (analytical)
Exp. duration:
60 min
Remarks on result:
other: based on hydrogen peroxide (pure)
Mortality:
There were no mortalities observed in this study.
Clinical signs:
other: Only sensory irritation was noted in the animals exposed to acetic acid, hydrogen peroxide as well as pure and a mixture of peroxyacetic acid.
Body weight:
No influence on body weight was reported.
Gross pathology:
Not performed

RD50 -determinations:


Acetic acid:


The onset of the response was rapid and reached a maximum within the first 2 min. There was no reductions in the degree of the response. For each concentration tested, the response of the animals was characteristic of sensory irritation. The break in respiration was observed at the start of the expiratory phase of respiration. There was no indication of pulmonary irritation, i.e. a characteristic pause present at the end of expiration. Recovery was rapid after the end of exposure and after 15 min., respiration rates reached 86 – 98 % of control values (i.e. before exposure start). The RD50 for acetic acid and the corresponding 95 % confidence interval were calculated to be 227 ppm (560 mg/m3).


 


Hydrogen peroxide:


The onset of the response was rapid but not as fast as observed for acetic acid especially at lower concentrations. The response remained steady throughout the 60 min exposure period. After termination of exposure, recovery was rapid and dependent on the concentration applied. After a recovery period of 15 min, respiration rates reached 74 – 98 % of control values which were obtained prior to exposure start.and reached a maximum within the first 2 min. There was no reductions in the degree of the response. For each concentration tested, the response of the animals was characteristic of sensory irritation. The break in respiration was observed at the start of the expiratory phase of respiration. There was no indication of pulmonary irritation, i.e. a characteristic pause present at the end of expiration. Recovery was rapid after the end of exposure and after 15 min., respiration rates reached 86 – 98 % of control values (i.e. before exposure start). The RD50 for hydrogen peroxide and the corresponding 95 % confidence interval were calculated to be 113 ppm (157 mg/m3).


 


“Pure” Peroxyacetic acid:


The onset of the response was rapid, particularly at the two highest concentrations where the maximum response was reached within the first 4 min. The effect  remained steady throughout the rest of the 60 min exposure period except for the lowest concentration where slight increase in the reduction of the respiration rate was observable between 30 min and 60 min of exposure. After termination of exposure, recovery was rapid and dependent on the concentration applied. After a recovery period of 15 min, respiration rates returned to 66 – 97 % of control values which were obtained prior to exposure start. The RD50 for pure peroxyacetic acid was calculated to be 5.4 ppm (17 mg/m3).


Peroxyacetic acid mixture:


The onset of the response and the time-effect profile for a mixture of peroxyacetic acid was essentially comparable to that of pure peroxyacetic acid. was rapid, particularly at the two highest concentrations where the maximum response was reached within the first 4 min. After termination of exposure, recovery was rapid and after a recovery period of 15 min, respiration rates returned to 80 – 97 % of control values which were obtained prior to exposure start. The RD50 for a mixture of peroxyacetic acid (i.e. in combination with acetic acid and hydrogen peroxide) was calculated to be 10.6 ppm (mixture) or 3.8 ppm (12 mg/m3) with respect to peroxyacetic acid only which is comparable to that of pure peroxyacetic acid.


 


RD50s of Acetic acid, hydrogen peroxide, a mixture of peracetic acid and pure acetic acid


































Substance



RD50



ppm



mg/m3



Acetic acid



227



560



Hydrogen peroxide



113



157



Pure Peroxyacetic acid



5.4



17



Mixture of Peroxyacetic acid*



10.6
(3.8 for peroxyacetic acid)



12
(peroxyacetic acid)



*: The peroxyacetic acid mixture contains peroxyacetic acid / acetic acid / hydrogen peroxide at a ratio of 36 %:53 %:11 %


 

Conclusions:
This study provides the basis for an argumentation as to why hydrogen peroxide does not contribute to the sensory irritation potential of PAA in PAA/HP/Acetic acid mixtures and needs therefore not to be considered for the assessment of the PAA risk from PAA/HP mixtures arising via the inhalation route. The RD50 values derived in this study are a reliable measure for the deduction of a TLV for PAA alone since the RD50 of 5.4 ppm determined for “pure” PAA (pure PAA was generated from a mixture of PAA/HP/Acetic acid by a special experimental set up and applying special conditions) was comparable to the fractional RD50 of 3.8 ppm for PAA determined from a mixture of PAA/HP/Acetic acid (ratio PAA:Acetic acid:HP = 36 %:53 %:11 %). From the study results it can be further concluded that the contribution of HP to the irritation potential of the mixture is negligible due to the low concentration of HP in the mixture in terms of its irritation potency. This is confirmed by an RD50 of 113 ppm determined for a 30 % HP solution versus an RD50 of 5.4 ppm for pure PAA alone and of 14 ppm for a PAA mixture containing 11 % HP only. This demonstrates that the RD50 of the mixture is mainly triggered by PAA (because a much higher HP concentration yielded also a higher RD50 as compared to the RD50 for PAA) and thus, the contribution of HP is negligible and does not have to be considered for the assessment of the PAA risk following inhalation.
On the basis of the RD50 values determined, the threshold limit value for peroxyacetic acid was calculated to be 0.2 ppm or 0.6 mg/m³.
Executive summary:

The results of the study demonstrated that the sensory irritation potency as derived by the RD50after a 1 hour exposure of male mice towards vapours of hydrogen peroxide, acetic acid and "pure" and a mixture of peroxyacetic acid increased in the order acetic acid  < hydrogen peroxide < mixture peroxyacetic acid < pure peroxyacetic acid. The RD50s derived for acetic acid (100 %), hydrogen peroxide (30 %) and a peroxyacetic acid mixture (containing 36 % peracetic acid, 53 % acetic acid, 11 % hydrogen peroxide) as well as pure peroxyacetic acid were 227 ppm (560 mg/m3), 113 ppm (157 mg/m3), 10.6 ppm (3.8 ppm or 12 mg/m3 with respect to peroxyacetic acid only) and 5.4 ppm (17 mg/m3), respectively.


 


Using the additivity rule, the theoretical RD50 was calculated to be 14.3 ppm for the peroxyacetic acid mixture (containing 36 % peroxyacetic acid) or 5.1 ppm with respect to peroxyacetic acid alone which is close to the experimental value of 3.8 ppm for peroxyacetic acid in the mixture. Although a contribution of hydrogen peroxide and acetic acid in the mixture cannot be entirely excluded, this is considered to be unlikely because the concentrations of these two chemicals are relatively low in terms of their irritant potency and when compared to the RD50s determined for 100 % acetic acid and 30 % hydrogen peroxide, respectively.


 


Furthermore, RD50values have been successfully shown to predict safe industrial exposures if sensory irritation is the most sensitive endpoint. Therefore, the RD50can be used as a basis for the determination of threshold limit values (TLVs). At 0.1 times the RD50, humans would experience a slight discomfort. Furthermore, 0.03 times the RD50 has been shown to correlate well with threshold limit values for a wide range of chemicals. Currently, no standards exist with respect to regulating exposure towards peroxyacetic acid. The short-term threshold limit should not exceed about 0.6 ppm or 1.8 mg/m3(0.1 times the RD50 of 5.4 ppm) and the TLV is estimated to be 0.2 ppm or 0.6 mg/m3.


 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
204 mg/m³ air
Quality of whole database:
Several reliable guideline studies with various dose concentrations of peracetic acid were avaialble.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Harlan CPB Zeist, The Netherlands
- Strain: Hsd/Cpb:WU Wistar
- Age: Not indicated
- Weight: 169-194 g (males), 145-172 g (females)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- Application volume: 2 mL/kg bw (2000 mg/kg bw)
- Area covered: aliquots of the test material were taken and applied over a strip gauze of about 40 cm^2
Doses:
2000 mg/kg of product (= 17.8 mg/kg of peracetic acid)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of post-exposure period: 14 days
- Removal of test substance: yes, after 24 hours the gauze patches were peeled off
- Examinations: Clinical signs and mortality (0.5, 1, 2, 3, 4 and 6 hours after dosing and then twice daily), local irritation on days 1, 3, 7 and 14, body weights (days 0, 7 and 14), gross necropsy at study termination.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: based on product (0.89% PAA), only dose tested; no mortalities
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 17.8 mg/kg bw
Remarks on result:
other: based on PAA (0.89% in product)
Mortality:
No mortalities.
Clinical signs:
other: Signs of mild irritation in most animals (white and/or red spots on treated skin, complete recovery after 12 days)
Gross pathology:
One female showed a maculate thymus. This was not considered to be a treatment related effect. No other findings.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 after dermal application of the test material is greater than 2000 mg/kg bw (corresponding to greater than 17.8 mg/kg bw peracetic acid). No classification with respect to acute dermal toxicity is required.
Executive summary:

In a study to assess the acute dermal toxicity of PAA a single dermal dose of 2000 mg/kg bw was applied under an occlusive dressing to the shaved intact skin of groups of five male and five female Wistar rats. The animals were weighed one day before dosing, at the day of dosing and at 2, 7 and 14 days after treatment. Any sign of intoxication occurring during the 14-day observation period was recorded. Gross post-mortem examination was done in all rats at the end of the 14-day observation period.

None of the rats died within the 14-day observation period. White and/or red spots were noted on the treated skin after removal of the bandage. These spots got brown and encrusted during the observation period. The skin symptoms subsided after 12 days. No other clinical signs were observed. Transient weight loss was observed in both sexes in the first few days of the study. Thereafter body weight gain appeared to be normal. This transient weight loss was considered to be partly a consequence of stress induced by the bandaging procedure (the study design) and partly consequence of stress induced by the irritating properties of the test material. At autopsy, no treatment related abnormalities were recorded for any of the animals.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Ray Nicholas Rabbitry, Lumberton, TX, USA
- Age: young adult
- Weight at study initiation: 2.200 - 3.350 kg (male), 2.250-3.200 kg (female)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- Area covered: 8 x 4 inch, (approximately 20 x 10 cm)
- Concentration in vehicle: All animals were treated with undiluted test substance. An individual dose was calculated for each animal.
- Application volume: 0.433, 1.75, 1.99 mL/kg bw (500, 2020, 2293 mg/kg bw)
- Removal of test substance: after 24 hours, the wrappings were removed, the test sites were gently washed with water
Duration of exposure:
24 hours
Doses:
500, 2020 and 2293 mg/kg bw of the product Proxitane WW12
(58, 236 and 268 mg/kg bw of peracetic acid)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 14 days
- Examinations: Mortality, clinical and behavioural signs of toxicity (3 times on day 0, at least once daily thereafter), body weights (day –1, 7 and 14 or at discovery of death), signs of dermal irritation (1 hour after removal of wrappings and on days 4, 7, 10 and 14), gross necropsy performed in all animals at study termination.
Statistics:
The LD50 value was calculated by a computer program utilizing probit analysis.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 957 mg/kg bw
Based on:
test mat.
95% CL:
1 757 - 2 181
Remarks on result:
other: based on product (11.7% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
228.8 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: based on PAA (11.7% in product)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 912 mg/kg bw
Based on:
test mat.
95% CL:
1 583 - 2 310
Remarks on result:
other: based on product (11.7% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
223.5 mg/kg bw
Based on:
act. ingr.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 990 mg/kg bw
Based on:
test mat.
95% CL:
1 850 - 2 140
Remarks on result:
other: based on product (11.7% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
232.6 mg/kg bw
Based on:
act. ingr.
Mortality:
For mortalities please refer to the table below.
Clinical signs:
other: There were no adverse clinical signs except of decreased activity in all dose groups, which had subsided by day 4 in surviving animals. Slight to severe oedema, atonia, blanching, bleeding (only in high dose), coriaceousness, desquamation, eschar, sloughi
Gross pathology:
No effects in surviving animals. Animals that died during the observation period showed discoloured ears matted chin hair, nasal and anal/genital discharge, atelectasis of lungs, air bubbles in major blood vessels and heart.

Table 1: Animal assignment to study groups and mortalities

Dose level

Mortalities / Treated animals

mg/kg bw

mL/kg bw

Males

Females

Combined

500

0.433

0 / 5

0 / 5

0 / 10

2020

1.75

3 / 5

3 / 5

6 / 10

2293

1.99

4 / 5

5 / 5

9 / 10

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute dermal LD50 for Proxitane WW12 in rabbits is 1912 mg/kg bw in males, 1990 mg/kg bw in females and 1957 mg/kg bw overall. The product is considered to be harmful in contact with skin (Xn, R21).
Executive summary:

The test substance Proxitane WW12 was evaluated for its dermal toxicity potential when undiluted doses at levels of 500, 2020 and 2293 mg/kg bw were applied to the intact skin of male and female albino rabbits and occlusively covered. After 24 hours, the cover and test substance were removed and the animals observed for mortality, clinical signs, dermal irritation and body weight development for an observation period of 14 days. A gross necropsy was performed in all animals at study termination.

No mortality occurred at the 500 mg/kg bw level. The only clinical sign was activity decrease in all dose groups, which was no longer evident in surviving animals by day 4. Signs of skin irritation included atonia, blanching, coriaceousness, oedema, erythema, eschar, necrosis and sloughing, which were seen in all dose groups. Additionally bleeding was observed in the highest dose group. There was an apparent effect on body weight gain in four surviving animals, three males (two in the lowest, one in the highest dose group) and one female of the lowest dose group. Abnormal necropsy findings occurred only in the animals dying during the study and pertained to the ears, muzzle, anal/genital areas, lungs, heart and major blood vessels.

The acute dermal LD50 for Proxitane WW12 in rabbits is 1912 mg/kg bw in males, 1990 mg/kg bw in females and 1957 mg/kg bw overall corresponding to 223.5, 232.6 and 228.8 mg/kg bw based on peracetic acid, respectively.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Ray Nicholas Rabbitry, Lumberton, TX, USA
- Age: Young adult
- Weight at study initiation: 2.375-3.000 kg (male), 2.400-3.125 kg (female)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- Area: 8 x 4 inch, (approximately 20 x 10 cm)
- Concentration in vehicle: all animals were treated with undiluted test substance. An individual dose was calculated for each animal
- Application volume: 0.445, 0.891, 1.80 mL/kg bw (500, 1000, 2020 mg/kg bw)
- Removal of test substance: after 24 hours, the wrappings were removed, the test sites were gently washed with water
Duration of exposure:
24 hours
Doses:
500, 1000 and 2020 mg/kg bw of the product Proxitane AHC
(24, 49 and 99 mg/kg bw of peracetic acid)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Post-exposure period: 14 days
- Observations: mortality, clinical and behavioural signs of toxicity (3 times on day 0, at least once daily thereafter), body weights (day –1, 7 and 14 or at discovery of death), signs of dermal irritation (1 hour after removal of wrappings and on days 4, 7, 10 and 14), gross necropsy performed in all animals at study termination.
Statistics:
The LD50 was calculated by a computer program utilizing probit analysis.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 147 mg/kg bw
Based on:
test mat.
95% CL:
756 - 1 738
Remarks on result:
other: based on product (4.89% PAA)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
56.1 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: based on PAA (4.89% in product)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 280 mg/kg bw
Based on:
test mat.
95% CL:
630 - 2 601
Remarks on result:
other: based on product (4.89% PAA)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
62.6 mg/kg bw
Based on:
act. ingr.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 040 mg/kg bw
Based on:
test mat.
95% CL:
528 - 2 047
Remarks on result:
other: based on product (4.89% PAA)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
50.9 mg/kg bw
Based on:
act. ingr.
Mortality:
Please refer to the table below.
Clinical signs:
other: Clinical signs were observed in all dose groups and included activity decrease, diarrhoea, lateral recumbency, nasal discharge, ptosis, salivation and star-gazing, which had completely resolved in all surviving animals on day 6. Well-defined to severe ery
Gross pathology:
No effects in surviving animals. Animals that died during the observation period showed wet, matted and/or stained muzzle, urogenital and anal areas, discoloured ears, air in blood vessels, heart and pericardium, fluid in pericardium, discolouration of lungs, mesentery, spleen and thymus.

Table 1: Animal assignment to study groups and mortalities

Dose level

Mortalities / Treated animals

mg/kg bw

mL/kg bw

Males

Females

Combined

500

0.445

1 / 5

1 / 5

2 / 10

1000

0.891

1 / 5

1 / 5

2 / 10

2020

1.80

4 / 5

5 / 5

9 / 10

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute dermal LD50 for Proxitane AHC in rabbits is 1280 mg/kg bw in males, 1040 mg/kg bw in females and 1147 mg/kg bw overall. The product is therefore considered to be harmful in contact with skin.
Executive summary:

The test substance Proxitane AHC was evaluated for its dermal toxicity potential when undiluted doses at levels of 500, 1000 and 2020 mg/kg bw were applied to the intact skin of male and female albino rabbits and occlusively covered. After 24 hours, the cover and test substance were removed and the animals observed for mortality, clinical signs, dermal irritation and body weight development for an observation period of 14 days. A gross necropsy was performed in all animals at study termination.

Mortalities occurred at all dose levels during the study. Clinical signs included activity decrease, diarrhoea, lateral recumbency, nasal discharge, ptosis, salivation and star-gazing. These had completely resolved in all surviving animals on day 6. Signs of skin irritation included severe erythema, slight to severe oedema, atonia, blanching, bleeding, coriaceousness, desquamation, eschar, fissuring, sloughing and necrosis. There were no significant effects on the body weights. There were no pathological effects in surviving animals revealed by necropsy. Animals that died during the observation period showed wet, matted and/or stained muzzle, urogenital and anal areas, discoloured ears, air in blood vessels, heart and pericardium, fluid in pericardium, discolouration of lungs, mesentery, spleen and thymus.

The acute dermal LD50 for Proxitane AHC in rabbits is 1280 mg/kg bw in males, 1040 mg/kg bw in females and 1147 mg/kg bw overall corresponding to 62.6, 50.1 and 56.1 mg/kg bw based on peracetic acid, respectively.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 147 mg/kg bw
Quality of whole database:
Several reliable guideline studies with various dose concentrations of peracetic acid were avaialble.

Additional information

Acute toxicity: oral


A number of oral acute toxicity studies were carried out in rats using different products containing concentrations of PAA ranging from 0.15 to 35%. The studies were carried out in accordance with standard OECD/EU/US-EPA and international GLP guidelines.


Two studies were available, where PAA in concentrations <1% were tested. In the first one conducted by Freeman (1991a) rats were dosed with a solution containing 0.15 % peracetic acid at a dosage level of 5000 mg/kg of the product in a limit test. All animals remained healthy throughout the study and no internal lesions were observed in any animal at necropsy. The LD50 is >5000 mg/kg bw based on the product.


In the second study, rats were dosed with a peracetic acid solution with a concentration of 0.89% at dosage levels of 514, 1027 and 2054 mg/kg of the product, the LD50 value derived is > 2000 mg/kg bw (combined) (Den Besten, 1994).


Several studies were performed with products containing peracetic acid ranging from 2.6 - 6.11%, which showed LD50 values ranging from 185 to 3622 mg/kg bw based on the product (Rondot, 1984; Kynoch and Mullins, 1985; Kuhn, 1996a; Freeman, 1998; Haynes and Brightwell, 1998; Harrod, 1993). The most frequently observed clinical effects during the studies consisted of piloerection, respiratory difficulties, reduced activity and diarrhoea. The main observed effects at necropsy were abnormalities in the gastrointestinal tract including distended stomach and some changes in adjacent organs, e.g. liver. Similar effects were observed in studies with products with peracetic acid concentrations ranging from 10 - 11.7%, with LD50 values ranging from 652 to 2540 mg/kg bw based on the product (Kuhn, 1996b, Degussa, 1977).


Two studies with products containing PAA with concentrations of 15 and 17% were reported (Degussa, 1982; Morris, 1995), with LD50 values of 1026 and 1780 mg/kg bw, respectively, based on the product. The main clinical signs observed were oral and ocular discharges, respiratory distress and abdominal distention. The gross necropsy findings in the animals that died during the observation period in all these studies were those generally seen in response to the oral administration of a severely irritating and corrosive material.


In one study, a product containing 35% peracetic acid was tested. The LD50 value was between 50 and 500 mg/kg bw based on the product, as 10/10 and 1/10 died at these dose levels, respectively (Freeman, 1987).


Based on the component peracetic acid, the lowest LD50 was 9.0 mg/kg bw (Kuhn, 1996a), but on the other hand also LD50 values higher than 200 mg/kg bw have been reported. The variability of the LD50 determinations for similar products is probably due to methodological differences, particularly differences in the peracetic acid concentration and volume of the test material solutions applied by gavage. If the stock solution was diluted and a constant volume was administered, the toxicity was generally lower as compared to studies where undiluted test material was administered and/or volumes increasing with higher dose levels. So the LD50 was 185 mg/kg bw for a product containing 4.89% peracetic acid applied undiluted with volumes ranging from 0.04 to 4.5 ml/kg bw (Kuhn, 1996a), whereas the LD50 values ranged from 1270 to 1922 mg/kg bw in the other studies conducted with similar products (4.5 - 6.11% peracetic acid), but administered in higher (fixed) volumes containing lower concentrations of peracetic acid. In the study showing the highest LD50 (3622 mg/kg bw), coconut oil was used as vehicle, whereas water was used in all other studies. Similar differences were seen in the other study conducted by Kuhn (1996b) with a product containing 11.7% peracetic acid. Thus, it can be concluded that the toxicity is higher when tissue (including the GIT) is damaged due to the corrosive properties of peracetic acid at higher concentrations.


Interestingly, in the studies conducted by Kuhn (1996a, b) gas in the GIT was found on gross pathological examination. This finding supports the assumption made to explain the local irritation of trachea and lungs observed in the subchronic rat study conducted by Gaou (2003).


Overall it can be concluded that for peracetic acid concentrations <1% the oral LD50 is >2000 mg/kg bw, for peracetic acid concentrations of 2.6 - 17% the oral LD50 is from 185 to 3622/kg bw, and from concentration of ≥35 %, the oral LD50 is 50-500 mg/kg bw, respectively.


 


Acute toxicity: inhalation


The available acute inhalation studies with aerosols and vapour derived from different peracetic acid solutions suffered on the one hand from the general difficulty of generating and maintaining a stable atmosphere of peracetic acid, but also on the other hand of the difficulties to measure accurately the composition of the test atmosphere and particle size of the aerosol. The reported LC50 values should be therefore treated with circumspection. However, the common finding of those studies was local irritation of the respiratory tract, which seems more pronounced with aerosols than vapours.


In that sense, the following two studies testing peracetic acid at concentrations of 5% and 36%, respectively, were selected as key studies. While a number of available supporting studies show generally lower toxicity values (if derived), these are not discussed in detail.


In a GLP guideline study, Janssen and Van Doom (1994) tested a 5 % solution of peracetic acid in rats exposed nose-only to aerosols containing measured concentrations of 87, 163, 185 and 267 mg peracetic acid/m³. The 4 -hour LC50 was 204 mg peracetic acid/m³ (4080 mg/m³ based on product). Mortalities were observed only in the two highest dose groups. Clinical signs consisted of apathy, respiratory distress, reduced respiratory rates, decreased fear reaction, freezing and reduced locomotion activity. No macroscopic alterations were seen at necropsy carried out at the end of the observation period.


In addition, the study conducted by Gagnaire (2002) was selected as key study, in which the irritating power of "pure" peracetic acid and commercially available peracetic acid (a mixture of peracetic acid, acetic acid and hydrogen peroxide) was evaluated. Effects were further compared to that of acetic acid and hydrogen peroxide using a quantitative methodology initially developed to test the sensory irritation properties of airborne chemicals in mice. The method used was based on the observation that irritants stimulate the trigeminal nerve endings in the nasal mucosa of oronasally exposed mice which causes a characteristic reflex leading to a decreased respiratory rate. The decrease is directly related to the exposure concentration. The concentration causing a 50 % decrease in the respiratory rate, i.e. the RD50, was used to compare the irritant potencies of peracetic acid, acetic acid and hydrogen peroxide, respectively, and to establish acceptable exposure levels. RD50 values have been successfully shown to predict safe industrial exposures if sensory irritation is the most sensitive endpoint. Therefore, the RD50 can be used as a basis for the determination of threshold limit values (TLVs).


Following this, the results of this study demonstrated that the sensory irritation potency as derived by the RD50 after a 1 hour exposure of male mice towards vapours of hydrogen peroxide, acetic acid a mixture of peracetic acid and pure paracetic. The RD50s derived for acetic acid (100%), hydrogen peroxide (30%) and a peracetic acid mixture (containing 36% peracetic acid, 53% acetic acid, 11% hydrogen peroxide) as well as pure peracetic acid were 227 ppm (560 mg/m3), 113 ppm (157 mg/m3), 10.6 ppm (3.8 ppm or 12 mg/m3 with respect to peracetic acid only) and 5.4 ppm (17 mg/m3), respectively. Using the additivity rule, the theoretical RD50 was calculated to be 14.3 ppm for the peracetic acid mixture (containing 36% peracetic acid) or 5.1 ppm with respect to peracetic acid alone which is close to the experimental value of 3.8 ppm for peracetic acid in the mixture. Although a contribution of hydrogen peroxide and acetic acid in the mixture cannot be entirely excluded, this is considered to be unlikely because the concentrations of these two chemicals are relatively low in terms of their irritant potency and when compared to the RD50s determined for 100% acetic acid and 30% hydrogen peroxide, respectively.


Together the data of the available acute inhalation toxicity studies revealed the calculated LC50 of 204 mg /m³ for 100% PAA. Moreover, a RD50 of 5.4 ppm was estimated, which is used for the risk assessment.


 


Acute toxicity: dermal


Several dermal toxicity studies were carried out in rats and rabbits with aqueous solutions of peracetic acid at concentrations ranging from 0.15 to 17 %. The studies were carried out in accordance with standard OECD/EU/US-EPA and international GLP guidelines. The acute dermal LD50 of formulations containing 5 - 15% peracetic acid was greater than 400 mg/kg bw in the rat and between 200 and 2000 mg/kg bw in the rabbit if based on the product. During many studies only one dose was tested, which did not result in any mortality. However, during the studies of Kuhn (1996c,d) mortality was found and they reported LD50 values of 1147 mg/kg bw based on the product (4.89% PAA) and 1957 mg/kg bw based on the product (11.7% PAA) for rabbits, corresponding to 56.1 and 228.8 mg/kg bw peracetic acid, respectively. It is important to stress out that the observed dermal toxicity depends on the degree of skin damage caused by the different peracetic acid solutions, since the corrosive properties of PAA may compromise the integrity of the skin. Based on this, the overall data suggest a dermal LD50 of >2000 mg/kg bw for peracetic acid <1% and a dermal LD50 of >1147 for peracetic acid at concentrations ≥1%.

Justification for classification or non-classification

The available data on acute oral, inhalative and dermal toxicity of peracetic acid meet the criteria for classification according to Regulation (EC) 1272/2008. Based on available data, PAA is classified and labelled for acute oral toxicity (category 3), acute dermal toxicity (category 4) and acute inhalation toxicity (category 2) according to Regulation (EC) No 1272/2008 (CLP), as amended for the seventeenth time in Regulation (EU) 2021/849.