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Administrative data

Description of key information

For OO-tert-butyl monoperoxymaleate (target substance) data is available to assess the acute toxicity of two routes. In an acute oral toxicity study conducted according to OECD 401, 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. The animals were observed for 15 days. Due to the mortality distribution, oral LD50 values of 449 mg/kg (males), 234 mg/kg (females), and 252 mg/kg bw for both sexes could be obtained.

In an acute dermal toxicity study similar to OECD 402, groups of young adult male and female Sprague-Dawley rats (5/sex) were dermally exposed to OO-tert-butyl monoperoxymaleate for 24 hours to 10% of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days. Under the conditions of this test, the acute dermal LD50 of OO-tert-butyl monoperoxymaleate was estimated to be greater than 2000 mg/kg bw in the rat. 

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:
1993-02-01 to 1993-05-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
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
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
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)
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)

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

-

-

-

-

-

-

-

-

-

-

-

-

-

-

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
252 mg/kg bw
Quality of whole database:
Guideline study

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:
1995-10-5 to 1996-01-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
The relative humidity (38-79%) exceeded the range specified in the protocol (40-70%). The p.m. mortality check was inadvertently not documented on study day 10 (10/29/95).
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: Geneseo, NY
- Lot/batch No.of test material: 8968525407
- Expiration Date: March 10, 1996

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Below 100˚F
- Solubility of the test substance: Slight

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No prior treatment. The test article was administered as received from the Sponsor.
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Sprague - Dawley Crl : CD BR VAF / Plus rats were used
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult
- Weight at study initiation: Males: 285-305 g, females: 240-257 g
- Housing: Animals were housed individually in suspended stainless steel cages. Housing and care was based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.
- Diet (e.g. ad libitum): ad libitum, Purina Certified Rodent Chow #5002
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 61 - 73 ˚F
- Humidity (%): 38-79
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: 10
- Type of wrap if used: plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, residual test item was removed using gauze moistened with distilled water
- Time after start of exposure: 24 h

TEST MATERIAL
- Constant volume or concentration used: yes
Duration of exposure:
approx. 24 h
Doses:
2000 mg / kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations: Test animals were observed for clinical abnormalities two times on study day 0 (postdose) and daily thereafter (days 1-14). A mortality check was performed twice daily, in the morning and afternoon. Dermal observations were made following patch removal on study day 1 and daily thereafter days (2 - 14).
- Frequency of weighing: Individual body weights were obtained prior to dosing on day 0, on days 7 and 14 and at the time of death for any animal dying on study (except those that die on day 0)
- Necropsy of survivors performed: yes
Statistics:
The LD50 value was estimated as follows:
< 50% mortality: LD50 was estimated as greater than the administered dose.
= 50% mortality: LD50 was estimated as equal to the administered dose.
> 50% mortality: L050 was estimated as less than the administered dose.

Body weight means and standard deviations were calculated separately for males and females for each limit level administered.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One animal was found dead on Day 2.
Clinical signs:
Most notable clinical abnormalities observed during the study included urine stain and dark material around the facial area, observed within the first three days of the study. For the animal that died, the clinical observations included decreased activity, wobbly gait, apparent hypothermia, urine stain, rough haircoat and dark material around the facial area. Dermal irritation was noted at the site of test article application for all animals.
Body weight:
Body weight loss was noted for three female rats during the study day 0-7 interval and one female rat during the study day 7-14 interval. Body weight gain was noted for all other surviving animals during the test period.
Gross pathology:
For the animals that died, the most notable necropsy findings observed dark red mandibular lymph nodes, reddened mucosa in the stomach and congested meningeal vessels in the brain. No gross internal findings were observed at necropsy on day 14 for the surviving animals.

Table 1: Mortality during the limit test for the test item

Dose (mg/kg bw)

No. Dead / No. Dosed

 

Males

Females

Combined

2000

0 / 5

1 / 5

1 / 10

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, the acute dermal LD50 of OO-tert-butyl monoperoxymaleate (25%) was estimated to be greater than 2000 mg/kg in the rat.
Executive summary:

In an acute dermal toxicity study, similar to OECD 402, groups of young adult male and female Sprague – Dawley rats (5/sex) were dermally exposed to OO-tert-butyl monoperoxymaleate (25%) for 24 hours to 10% of body surface area at a dose of  2000 mg/kg bw.  Animals then were observed for 14 days. Under the conditions of this test, the acute dermal LD50 of OO-tert-butyl monoperoxymaleate (25%) was estimated to be greater than 2000 mg/kg in the rat. 

Most notable clinical abnormalities observed during the study included urine stain and dark material around the facial area, observed within the first three days of the study. For the animal that died, the clinical observations included decreased activity, wobbly gait, apparent hypothermia, urine stain, rough haircoat and dark material around the facial area. Dermal irritation was noted at the site of test article application for all animals.

Body weight loss was noted for three female rats during the study day 0-7 interval and one female rat during the study day 7-14 interval. Body weight gain was noted for all other surviving animals during the test period.

For the animals that died, the most notable necropsy findings observed dark red mandibular lymph nodes, reddened mucosa in the stomach and congested meningeal vessels in the brain. No gross internal findings were observed at necropsy on the last day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Comparable to guideline study

Additional information

The acute dermal toxicity study was performed with a 25% solution of the target substance. Data for the substance as such (50% in phlegmatizer) are not available. However, since the mortality at 25% was 1/10 and the substance is marketed as 50% dispersion (phlegmatized), it can be assumed that doubling the concentration will not increase the mortality to 5 out of ten. Therefore, especially in the framework of the 3R principle by Russell and Burch, it would scientifically not be justified to conduct a dermal acute oral toxicity study.

Justification for classification or non-classification

Based on the available data, the target substance OO-tert-butyl monoperoxymaleate has to be classified as Toxic if swallowed (Acute Tox. 3, H301) according to CLP criteria. No classification is warranted for acute dermal toxicity.