Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-02-01 to 1993-05-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
TEST MATERIAL
- Identification: Perkadox PF
- Chemical name: tert butyl monoperoxymaleate
- CAS No.: 1931-62-0
- Batch No.: 221190 ex PDD
- Purity: 97.8 - 98.0 % m/m
- Appearance: white solid
- Storage: dark, refrigerated
- Expiry Date: 1993-07-01

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Number of animals per group: 5 males and 5 females
- Age at start of treatment: approx. 7 - 12 weeks
- Body weight at start of treatment: males 256 - 324 g, females 188 - 238 g
- Identification: Earmark
- Acclimatisation: 27 - 37 days before start of treatment under laboratory conditions
- Housing: 5 per sex to a cage (labelled polycarbonate cages containing purified sawdust as bedding materials (Woody SPF, supplied by B.M.I., Someren, The Netherlands)
- Diet: ad libitum, standard pelleted laboratory animal diet (Kliba 343 from Klingantalmühle AG, Kaiseraugst, Switzerland)
- Water: ad libitum, tap water

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 22 °C
- Humidity: 30 - 55 %
- Photoperiod (hrs dark / hrs light): 12/12
- Air changes per hour: 15

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1 % aqueous
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION: The formulations were prepared immediately prior to dosing. The test substance was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Homogenicity of the test substance in vehicle was obtained using a mechanical stirrer, electric blender or by shaking.
Doses:
200, 1000, 2000 and 5000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days

OBSERVATIONS
- Weighing: Days 1 (pre-administration), 8 and 15 and at death (if found dead after day 1)
- Mortality/Viability: Twice daily. The time of death was recorded as precisely as possible
- Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter. The time of onset, degree and duration were recorded
- Necropsy of survivors performed: yes, all animals were sacrificed by oxygen/carbon dioxide asphyxiation and examined
Statistics:
LD50 values and associated 95% confidence interval, the slope of the dose mortality curve were calculated using Probit Analysis (SAS Technical Report: P-179, Additional SAS/STAT Procedures, Release 6.03, Chapter 4, the PROBIT Procedure)

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
234 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated value
Sex:
male
Dose descriptor:
LD50
Effect level:
449 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated value
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
252 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated value
Mortality:
The following mortality rates were observed:
200 mg/kg bw: males: 0/5; females: 1/5

1000 mg/kg bw: males: 5/5, females: 5/5

2000 mg/kg bw: males: 5/5; females: 5/5

5000 mg/kg: males: 5/5; females: 5/5

The deaths occured between day 1 and 4.
Clinical signs:
200 mg/kg bw: lethargy, hunched posture, rales, rough coat
1000 mg/kg bw: lethargy, hunched posture, ventro-lateral recumbency, temors, uncoordinated movements, rough coat
2000 mg/kg bw: lethargy, hunched posture, ventro-lateral recumbency
5000 mg/kg bw: lethargy, ventro-lateral recumbency (females only)

Surviving animals had recovered on days, 3, 11 or 13.
Body weight:
Body weight loss was noted in one surviving female and low body weight gain was noted in another surviving female over the first week of the observation period. Low body weight gain was noted in one surviving male and in two surviving females over the second week. The other surviving animals showed normal body weight gain over the study period.
Gross pathology:
Macroscopic post mortem examination of the animals that died during the study revealed the following abnormalities in each group:

200 mg/kg bw: No findings
1000 mg/kg bw: Gelatinous contents in small intestines, reddish discolouration of dilated small intestines, pale colouration of granular stomach, watery contents in enlarged stomach, haemorrhage of thymus
2000 mg/kg bw: Gelatinous contents in small intestines, reddish discolouration of dilated small intestines, pale colouration of granular stomach, watery contents in enlarged stomach
5000 mg/kg bw: Pale colouration of grandular stomach and duodenum, milky-cloudy fluid contents in stomach, thickening of limiting ridge in stomach, gray-white contents in duodenum, haemorrhage of thymus, pelvic dilation of right kidney

Renal pelvis dilation is commonly noted among rats of this age and strain and therefore considered not to have arisen as a result of treatment with the test substance.

Macroscopic post mortem examination of the surviving animals at termination revealed the following abnormalities:
200 mg/kg bw: granulated gray-white surface of kidneys (one female)

Any other information on results incl. tables

Table 1: Number of decedents after treatment - males

Test day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours after treatment

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Group 1 (200 mg/kg)

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Group 2 (1000 mg/kg)

-

2

-

2

1

-

-

-

-

-

-

-

-

-

-

-

-

Group 3 (2000 mg/kg)

-

1

-

4

-

-

-

-

-

-

-

-

-

-

-

-

-

Group 4 (5000 mg/kg)

-

5

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Table 2: Number of decedents after treatment - females

Test day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours after treatment

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Group 1 (200 mg/kg)

-

-

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

Group 2 (1000 mg/kg)

-

1

-

4

-

-

-

-

-

-

-

-

-

-

-

-

-

Group 3 (2000 mg/kg)

-

3

-

2

-

-

-

-

-

-

-

-

-

-

-

-

-

Group 4 (5000 mg/kg)

-

4

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The presented study finds that OO-tert-butyl monoperoxymaleate is toxic and is classified under "Category 3" according to the UN GHS Criteria.
Executive summary:

In an acute oral toxicity study conducted according to OECD guideline 401, twenty fasted female and twenty fasted male Wistar rats (5/sex/dose) were given a single oral dose of OO-tert-butyl monoperoxymaleate (> 97% purity), suspended in a 1% aqueous carboxymethyl cellulose, at a dose of 200, 1000, 2000 and 5000 mg/kg bw and were observed for 15 days. Due to the mortality distribution, estimated oral LD50 values of 449 mg/kg (males), 234 mg/kg (females), and 252 mg/kg bw for both sexes could be obtained.