Sodium long chain alkyl salicylate

Endpoint summary

Description of key information

ACUTE ORAL
LD50 300 to 2000 mg/kg bw (rat); OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF 12 Nousan, Notification No 8147
ACUTE DERMAL
LD50 > 2000 mg/kg bw (rat); OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF 12 Nousan, Notification No 8147

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 August 2014 to 09 September 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF, 12 Nousan, Notification No 8147, November 2000

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar strain Crl:WI (Han) (outbred, SPF-Quality)
- Age at study initiation: Approximately 8 to 9 weeks old
- Weight at study initiation: 147 to 169 g. Body weight variation did not exceed ± 20 % of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3 to 4 hours after administration of the test material. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labelled cages (height 18 cm) containing sterilised sawdust as bedding material and paper as cage-enrichment.
- Diet: Free access to pelleted rodent diet
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24 °C
- Humidity: 40 to 70 % (relative)
- Air changes: at least 10 air changes/hour
- Photoperiod: 12-hour light/12-hour dark cycle

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE:
- Specific gravity: 1.036
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at the testing facility and on test material data.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight

DOSAGE PREPARATION (if unusual): The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. The concentration of the test material in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.
In order to obtain homogeneity, the test material formulations were heated in a water bath with a maximum temperature of 77.5 °C for a maximum of 75 minutes. The test material formulations were allowed to cool down to a temperature of maximally 40 °C prior to dosing.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Starting dose = 2000 mg/kg bw. Substance initially assumed to be of low toxicity based on test on amixture containing the substance.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 animals were dosed at 2000 mg/kg bw. 6 animals were dosed at 300 mg/kg bw.

Control animals:

no

Details on study design:

- Study design: The toxicity of the test material was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. Initially, the test material was administered at 2000 mg/kg bw. In a stepwise procedure, two additional groups were dosed at 300 mg/kg bw.
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed for mortality and viability twice daily. Time of death was recorded as precisely as possible. Body weights were recorded on Day 1 (pre-administration of the test material), Days 8 and 15 and at death (if found dead after Day 1). At periodic intervals on the day of dosing (Day 1) and once daily thereafter until Day 15, animals were observed for clinical signs. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: Yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

No statistical analysis was performed as the method used is not intended to allow the calculation of a precise LD50 value.

Sex:

female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, two animals were found dead on day 2.
At 300 mg/kg, no mortality occurred.

Clinical signs:

other: At 2000 mg/kg, hunched posture, piloerection and/or diarrhoea were noted for the animals on Day 1. At 300 mg/kg, hunched posture, piloerection and/or diarrhoea were noted for the animals on Days 1 and 2.

Gross pathology:

At 2000 mg/kg, abnormalities of the stomach (glandular mucosa: several dark red foci; forestomach: irregular surface) and thymus (reddish discolouration) were found in both animals that died during the study. Additionally, in one of these animals gelatinous contents of the gastro intestinal-tract were found.
Furthermore, advanced autolysis was seen in both animals found dead. This finding was considered to be due to the time elapsed between death and macroscopic examination.
At 300 mg/kg, no abnormalities were found at macroscopic examination of the animals.

Other findings:

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.

Table 1: Body Weight Data (g)

Dose Group	Animal Number	Day 1	Day 8	Day 15
Group dosed with 2000 mg/kg bw	1	147*	-	-
	2	162	183	202
	3	164**	-	-
	Mean (SD)	158 (9)	183	202
First group dosed with 300 mg/kg bw	4	153	178	206
	5	153	190	197
	6	155	191	206
	Mean (SD)	154 (1)	186 (7)	203 (5)
Second group dosed with 300 mg/kg bw	7	169	203	213
	8	159	187	198
	9	161	180	194
	Mean (SD)	163 (5)	190 (12)	202 (10)

*Animal found dead on day 2. Body weight at death 139 g

**Animal found dead on day 2. Body weight at death 160 g

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the LD50 value was established to be within the range of 300 to 2000 mg/kg body weight and in accordance with OECD Guideline 423, the LD50 cut-off value was considered to be 1000 mg/kg.

Executive summary:

The potential of the test material to cause acute oral toxicity in the rat was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF 12 Nousan, Notification No 8147 under GLP conditions.

Initially, the test material was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure, two additional groups of three females were dosed at 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

At 2000 mg/kg, two animals were found dead on day 2. At 300 mg/kg, no mortality occurred.

At 2000 mg/kg, hunched posture, piloerection and/or diarrhoea were noted for the animals on Day 1. At 300 mg/kg, hunched posture, piloerection and/or diarrhoea were noted for the animals on Days 1 and 2.

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

At 2000 mg/kg, abnormalities of the stomach (glandular mucosa: several dark red foci; forestomach: irregular surface) and thymus (reddish discolouration) were found in both animals that died during the study, at macroscopic post mortem examination. Additionally, in one of these animals gelatinous contents of the gastro intestinal-tract were found. At 300 mg/kg, no abnormalities were found at macroscopic examination of the animals.

Under the conditions of this study the LD50 value was established to be within the range of 300 to 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

Two GLP studies are available to address this endpoint, though only one was conducted in accordance with standardised guidelines. Both were awarded a reliability score of 1 in accordance with the criteria for data quality set forth by Klimisch et al. (1997). The quality of the database is considered to be high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 October 2014 to 30 October 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF 12 Nousan, Notification No 8147

Deviations:

no

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:

TEST ANIMALS
- Strain: Wistar strain Crl:WI (Han) (outbred, SPF-Quality)
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: Males 257 to 292 g; females 195 to 209 g. Body weight variation did not exceed ± 20 % of the sex mean.
- Fasting period before study: No
- Housing: During acclimatisation, animals were group housed (cage height 18 cm). During the study, animals were individually housed in labelled cages (height 18 cm) containing sterilised sawdust as bedding material and paper as cage-enrichment.
- Diet: Free access to pelleted rodent diet
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24 °C
- Humidity: 40 to 70 % (relative)
- Air changes: at least 10 air changes/hour
- Photoperiod: 12-hour light/12-hour dark cycle

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: One day before exposure (Day -1) an area of approximately 5 x 7 cm on the back of each animal was clipped.
- % coverage: The test material was applied on an area of approx. 10 % of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The test material was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminium foil and elastic bandage. A piece of tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST MATERIAL
- Washing (if done): Dressings were removed and the skin cleaned of residual test material using tap water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 10 mL/kg body weight.
- Other: The test material was stirred on a magnetic stirrer during application. The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.
In order to obtain homogeneity, the test substance formulation was heated in a water bath with a maximum temperature of 73 °C for 63 minutes. The formulation was allowed to cool down to a temperature of maximally 40 °C prior to dosing.

VEHICLE
- Specific gravity: 1.036

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed for mortality and viability twice daily. The time of death was recorded as precisely as possible. Body weights were recorded on Day 1 (pre-administration of the test material), Days 8 and 15 and at death (if found dead after Day 1). At periodic intervals on the day of dosing (Day 1) and once daily thereafter until Day 15, animals were observed for clinical signs. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: Yes. At the end of the observation period, all animals were sacrificed by an oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: Descriptions of all internal macroscopic abnormalities were recorded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One male animal was found dead on Day 2 of the study (one day after treatment). No abnormality was noted at necropsy and the cause of death could not be determined.

Clinical signs:

other: Hunched posture was noted for four animals on Days 6 and/or 7 and for one animal between Days 6 and 10. General erythema, fissures, scales and/or scabs of the skin were seen in the treated skin-area, abdomen, left hindleg and/or flanks of the animals duri

Gross pathology:

Abnormalities of the liver (irregular surface) were found in one male and one female animal at macroscopic post mortem examination.
A diaphragmatic hernia of the left medial liver lobe was seen in one male animal. This finding is occasionally noted among rats of this age and strain and was therefore considered not toxicologically significant.
Macroscopic examination of the other animals did not reveal any abnormalities.

Table 1: Body Weight Data (g)

Dose Group	Animal Number	Day 1	Day 8	Day 15
Males dosed with 2000 mg/kg bw	1	287	275	310
	2	292	278	314
	3	292	278	327
	4	287	282	329
	5	257*	-	-
	Mean (SD)	283 (15)	278 (3)	320 (9)
Females dosed with 2000 mg/kg bw	6	195	186	204
	7	198	185	202
	8	209	211	225
	9	198	201	212
	10	196	192	203
	Mean (SD)	199 (6)	195 (11)	209 (10)

*Animal found dead on Day 2; body weight at death 257 g

 

Table 2: Clinical Signs

Parameter	Max Grade	Test Day
		1	2	3	4	5	6	7	8	9	10	11	12	13	14	15
Males
Animal 1 Erythema (ts) Scales (ts) Scabs (a) Scabs (lh) Scabs (ts)	4 3 3 3 3	- - - - -	1 - - - -	1 - - - -	- - - - -	- - - - -	- 2 - - 1	- 2 - - 1	- 2 2 1 1	- 2 - - 1	- 2 - - 1	- 2 - - 1	- 2 - - 1	- 2 - - 1	- 2 - - 1	- 1 - - -
Animal 2 Erythema (ts) Scales (a) Scales (ts) Scabs (tt)	4 3 3 3	- - - -	1 - - -	- - - -	- - - -	- - - -	- - 2 1	- - 2 1	- 1 2 1	- 1 2 1	- 1 2 1	- 1 2 1	- 1 2 1	- 1 2 1	- 1 2 1	- - 1 -
Animal 3 Hunched posture Erythema (a) Erythema (ts) Scales (a) Scales (ts) Scabs (a) Scabs (ts)	1 4 4 3 3 3 3	- - - - - - -	- - 1 - - - -	- - 2 - - - -	- - 1 - - - -	- - 1 - - - -	1 - - - 2 - 1	- - - - 2 - 1	- 1 - 1 2 1 1	- 1 - 1 2 1 1	- 1 - 1 2 1 1	- 1 - 1 2 1 1	- 1 - 1 2 1 1	- 1 - 1 2 1 1	- 1 - 1 2 1 1	- 1 - 1 1 - -
Animal 4 Hunched posture Erythema (ts) Fissures (ts) Scales (a) Scales (ts) Scabs (ts)	1 4 3 3 3 3	- - - - - -	- 1 - - - -	- 1 - - - -	- 1 - - - -	- 1 - - - -	1 1 1 - 2 -	1 1 1 - 2 1	- 1 - 1 2 1	- 1 - 1 2 1	- 1 - 1 2 1	- 1 - 1 2 1	- 1 - 1 2 1	- 1 - 1 2 1	- 1 - 1 2 1	- - - - 1 -
Animal 5 No clinical signs noted
Females
Animal 6 Erythema (ts) Scales (a) Scales (rf) Scales (ts) Scabs (lk)	4 3 3 3 3	- - - - -	1 - - - -	- - - - -	- - - - -	- - - - -	- - - 2 1	- - - - -	- 1 1 2 1	- 1 1 2 1	- 1 1 2 1	- 1 1 2 1	- 1 1 2 1	- 1 1 2 1	- 1 1 2 1	- - - - -
Animal 7 Hunched posture Erythema (ts) Fissures (ts) Scales (lh) Scales (ts) Scabs (lh) Scabs (ts)	1 4 3 3 3 3 3	- - - - - - -	- 1 - - - - -	- - - - - - -	- - - - - - -	- - - - - - -	1 - 1 - 2 - 1	1 - 1 - 2 - 1	- - - 1 3 1 1	- - - 1 3 1 1	- - - 1 3 1 1	- - - 1 3 1 1	- - - 1 3 1 1	- - - 1 2 1 1	- - - 1 2 1 1	- - - - 1 - -
Animal 8 Hunched posture Erythema (a) Erythema (ts) Fissures (lf) Fissures (ts) Scales (ts) Scabs (a) Scabs (lf) Scabs (rf) Scabs (ts) Hypersensitivity to touch (ts)	1 4 4 3 3 3 3 3 3 3 1	- - - - - - - - - - -	- - 1 - - - - - - - -	- - 1 - - - - - - - -	- - - - - - - - - - -	- - - - - - - - - - -	1 - - - - 2 - - - 1 -	1 - - 1 1 2 - - 1 2 1	- 1 - - - 1 1 1 1 1 -	- 1 - - - 1 1 1 1 1 -	- 1 - - - 1 1 1 1 1 -	- 1 - - - 1 1 1 1 1 -	- 1 - - - 1 1 1 1 1 -	- 1 - - - 1 1 1 1 1 -	- 1 - - - 1 1 1 1 1 -	- - - - - 1 - - - 1 -
Animal 9 Erythema (lh) Erythema (ts) Scales (lf) Scales (lh) Scales (ts)	4 4 3 3 3	- - - - -	- 1 - - -	- - - - -	- - - - -	- - - - -	- - - - 1	- - - - 1	- - 1 1 1	- - 1 1 1	- - 1 1 1	- - 1 1 1	- - 1 1 1	1 - 1 1 1	1 - 1 1 1	- - - - -
Animal 10 Hunched posture Erythema (a) Erythema (ts) Fissures (ts) Scales (a) Scales (ts) Scabs (lf) Scabs (ts) Hypersensitivity to touch (ts)	1 4 4 3 3 3 3 3 1	- - - - - - - - -	- - 1 - - - - - -	- - - - - - - - -	- - - - - - - - -	- - - - - - - - -	1 - - 2 - 3 - 1 1	1 - - 2 - 3 1 2 1	1 1 - - 1 3 1 2 -	1 1 - - 1 3 1 2 -	1 1 - - 1 3 1 2 -	- 1 - - 1 3 1 2 -	- 1 - - 1 3 1 2 -	- 1 - - 1 1 1 1 -	- 1 - - 1 1 1 1 -	- - - - - 1 - - -

ts = treated skin

a = abdomen

lh = left hindleg

rf = right flank

lf = left flank

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the LD50 value was found to exceed 2000 mg/kg bw.

Executive summary:

The potential of the test material to cause acute dermal toxicity in the rat was investigated in accordance with the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF 12 Nousan, Notification No 8147 under GLP conditions.

The test material was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. After the exposure period, dressings were removed and the skin cleaned of residual test material using tap water. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

One male animal was found dead on Day 2 of the study (one day after treatment). No abnormality was noted at necropsy and the cause of death could not be determined.

Hunched posture was noted for four animals on Days 6 and/or 7 and for one animal between Days 6 and 10. General erythema, fissures, scales and/or scabs of the skin were seen in the treated skin-area, abdomen, left hindleg and/or flanks of the animals during the observation period. The treated skin of two animals was hypersensitive to touch on Days 6 and/or 7.

All animals showed body weight loss or reduced body weight gain (two females) between Days 1 and 8. All animals gained body weight between Days 8 and 15. The changes in body weight in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Abnormalities of the liver (irregular surface) were found in one male and one female animal at macroscopic post mortem examination. Macroscopic examination of the other animals did not reveal any abnormalities.

Under the conditions of this study the LD50 value was found to exceed 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study was conducted in accordance with standardised guidelines under GLP conditions. It was assigned a reliability score of 1 in accordance with the criteria for data quality set forth by Klimisch et al. (1997). The quality of the database is therefore considered to be high.

Additional information

Acute Oral Toxicity

In the key study, the potential of the test material to cause acute oral toxicity in the rat was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF 12 Nousan, Notification No 8147 under GLP conditions.

Initially, the test material was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure, two additional groups of three females were dosed at 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

At 2000 mg/kg, two animals were found dead on day 2. At 300 mg/kg, no mortality occurred.

At 2000 mg/kg, hunched posture, piloerection and/or diarrhoea were noted for the animals on Day 1. At 300 mg/kg, hunched posture, piloerection and/or diarrhoea were noted for the animals on Days 1 and 2.

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

At 2000 mg/kg, abnormalities of the stomach (glandular mucosa: several dark red foci; forestomach: irregular surface) and thymus (reddish discolouration) were found in both animals that died during the study, at macroscopic post mortem examination. Additionally, in one of these animals gelatinous contents of the gastro intestinal-tract were found. At 300 mg/kg, no abnormalities were found at macroscopic examination of the animals.

Under the conditions of this study the LD50 value was established to be within the range of 300 to 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.

 

A supporting study is also available that was conducted using methodology similar to that outlined in the standardised guideline OECD 401 under GLP conditions.

Five male and 5 female F344 rats were exposed to a limit dose of the test material (supplied in mineral oil) of 2000 mg/kg bw.

None of the rats died and it was therefore concluded that the acute oral LD50 of undiluted EC# 701-403-0 was greater than 2000 mg/kg.

 

Acute Inhalation Toxicity

In accordance with Section 8.5.2. of Column 2 of Annex VIII of the REACH Regulation, the registrant proposes to waive the acute toxicity testing by the inhalation route on the grounds that exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and the possibility of exposure to aerosols, particles or droplets of an inhalable size.

 

Acute Dermal Toxicity

The potential of the test material to cause acute dermal toxicity in the rat was investigated in accordance with the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF 12 Nousan, Notification No 8147 under GLP conditions.

The test material was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. After the exposure period, dressings were removed and the skin cleaned of residual test material using tap water. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

One male animal was found dead on Day 2 of the study (one day after treatment). No abnormality was noted at necropsy and the cause of death could not be determined.

Hunched posture was noted for four animals on Days 6 and/or 7 and for one animal between Days 6 and 10. General erythema, fissures, scales and/or scabs of the skin were seen in the treated skin-area, abdomen, left hindleg and/or flanks of the animals during the observation period. The treated skin of two animals was hypersensitive to touch on Days 6 and/or 7.

All animals showed body weight loss or reduced body weight gain (two females) between Days 1 and 8. All animals gained body weight between Days 8 and 15. The changes in body weight in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Abnormalities of the liver (irregular surface) were found in one male and one female animal at macroscopic post mortem examination. Macroscopic examination of the other animals did not reveal any abnormalities.

Under the conditions of this study the LD50 value was found to exceed 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Two studies are available to address this endpoint. The key study was selected on the basis that it is fully compliant with standardised guidelines and was carried out under GLP conditions. Furthermore, a lower LD50 value was obtained for this study making it the key study for risk assessment purposes.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to acute toxicity via the dermal route. The substance requires classification via the oral route as Category 4 (H302: Harmful if swallowed).