Peracetic acid

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

There is no OECD guideline for the conduct of acute toxicity studies following intravenous administration; the procedures employed followed OECD guideline 401 (“Acute Oral Toxicity”)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Peracetic acid

EC Number:

201-186-8

EC Name:

Peracetic acid

Cas Number:

79-21-0

Molecular formula:

C2H4O3

IUPAC Name:

Peracetic acid generated by perhydrolysis of N-acetylcaprolactam by hydrogen peroxide in alkaline conditions

Test animals

Species:

mouse

Strain:

CF-1

Sex:

male

Details on test animals or test system and environmental conditions:

source: Winkelmann, Hannover

Administration / exposure

Route of administration:

intravenous

Vehicle:

physiological saline

Details on exposure:

Intravenous application
Injection duration: 1 minute

Doses:

Dose levels 158, 172, 186, 199, 251, 316, 398 mg/kg bw
Concentration in vehicle 15.8, 17.2, 18.6, 19.9, 25.1, 31.6, 39.8 mg/mL
Total volume applied 10 mL/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

Seven groups of 10 male CF 1 mice each received a single i.v. injection of P3 oxonia aktiv at dose levels of 158, 172, 186, 199, 251, 316, and 398 mg/kg bw, respectively, at a constant dosing volume of 10 mL/kg bw in physiological saline as the vehicle. Animals were regularly observed for clinical signs (immediately, 1, 6 and 24 hours after application and in intervals of 1 – 3 days until day 14) and mortality throughout the study. Body weights were determined on the day of administration and on days 7 and 14 of the study. A macroscopic examination of decedents and scheduled deaths was performed at the end of the study period. The study was terminated after a post-observation period of 14 days and a gross pathological examination was performed.

Statistics:

The intravenous LD50 was determined according to the method of J.T. Litchfield and F. Wilcoxon (J. pharm. Exptl. Ther. 96, 99-108 (1949)).

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

212 mg/kg bw

95% CL:

190.9 - 235.2

Remarks on result:

other: based on product (4.6% PAA)

Mortality:

see below

Clinical signs:

see below

Body weight:

see below

Gross pathology:

see below

Other findings:

see below

Any other information on results incl. tables

Clinical signs:

Signs of intoxication were notable directly after intravenous administration and recovery was seen within 24 hours after dosing. At lower dose levels only slight signs of intoxication were evident, at higher doses, however, severe signs of intoxication were evident:

-          158 mg/kg bw: moderately decreased spontaneous activity within 24 hours after treatment and moderate convulsions until 1 hour after treatment, moderate piloerection until 24 hours after treatment and slight to moderate tachypnoe until 6 hours after treatment.

-          172 mg/kg bw: moderately decreased spontaneous activity within 24 hours after treatment and moderate convulsions until 1 hour after treatment, marked piloerection until 24 hours after treatment and marked tachypnea until 1 hour after treatment (completely reversible after 6 hours).

-          186 mg/kg bw: moderately decreased spontaneous activity within 24 hours after treatment, distinct vocalisation directly after treatment, marked convulsions and moderate ataxia until 1 hour after treatment, marked piloerection and marked tachypnea within 24 hours after treatment.

-          199 mg/kg bw: markedly reduced spontaneous activity within 24 hours after treatment, distinct vocalisation and strong convulsions directly after treatment, marked ataxia within 6 hours after treatment, prone position moderate in degree directly after treatment, marked piloerection and strong tachypnea within 24 hours after treatment.

-          251 mg/kg bw: severely reduced spontaneous activity und severe ataxia within 24 hours after treatment, distinct vocalisation, marked convulsions, marked prone position and reduced ear reflex within 1 hour after treatment, slightly reduced corneal reflex directly after treatment, marked piloerection and strong tachypnea within 24 hours after treatment.

-          316 mg/kg bw markedly reduced activity and severe ataxia within 24 hours after treatment, severe vocalisation, convulsions and prone position within 1 hour after treatment, moderately decreased ear reflex, slightly reduced corneal reflex within 6 hours after treatment, marked piloerection and strong tachypnea within 24 hours after treatment

-          398 mg/kg bw: severe vocalisation directly after treatment, severe convulsions, severe prone position, severe piloerection and strong tachypnea, all animals died within 1 minute after treatment

 

In all dose groups, animals lost body weights until 24 hours after administration only. Thereafter, the body weight development of the surviving animals was considered to be normal.

Mortalities:

After single i.v. treatment with P3 oxonia aktiv, death was observed 5 – 6 minutes after administration of 172 and 186 mg/kg bw, 4 – 5 minutes after administration of 199 mg/kg bw, 3 minutes after administration of 251 mg/kg bw and 2 minutes after administration of 316 mg/kg bw. A dose of 398 mg/kg bw caused death 20 – 30 seconds after administration.

 

Pathology:

There were no macroscopic findings in decedents and scheduled deaths after 14 days.

 

LD50:

The LD₅₀ for P3 oxonia aktiv after a single i.v. administration to male CF 1 mice was determined to be 212 mg/kg bw (C.I: 190.9 – 235.2 mg/kg bw).

 

Table 1: Acute Toxicity (iv.) of P3 oxonia aktiv in Male CF 1 Mice

Dose [mg/kg bw]	Number of dead / number of investigated	Time of death (range)
158	0/10	‑
172	2/10	5 – 6 minutes
186	4/10	5 ‑ 6 minutes
199	6/10	4 ‑ 5 minutes
251	6/10	3 minutes
316	9/10	2 minutes
398	10/10	20 ‑30 seconds

 

 

 

 

 

Applicant's summary and conclusion

Conclusions:

The LD50 for P3 oxonia aktiv after a single i.v. administration to male CF 1 mice was determined to be 212 mg/kg bw (C.I: 190.9 – 235.2 mg/kg bw).

Executive summary:

Seven groups of 10 male CF 1 mice each received a single i.v. injection of P3 oxonia aktiv at dose levels of 158, 172, 186, 199, 251, 316, and 398 mg/kg bw, respectively, at a constant dosing volume of 10 mL/kg bw in physiological saline as the vehicle.

Following single i.v. administration of P3 oxonia aktiv to male CF 1 mice, death occurred at all dose levels except the low dose level of 158 mg/kg bw. Death was observed within 20 seconds until 6 minutes after injection. Clinical signs comprised decreased spontaneous activity, ataxia, tachypnea, vocalisation, convulsions, prone position and piloerection. The severity of clinical signs depended on the dose level given.

There were no gross pathological findings notable after necropsy of both decedents and scheduled deaths.