Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 4, 1990 - April 26, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Non-GLP study, however study was conducted in compliance with the Good Laboratory Practice Standards of the Environmental Protection Agency FIFRA, 40 CFR Part 160; the Environmental Protection Agency TSCA, 40 CFR part 792 and the OECD guideline 401.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Pesticide Assessment Guidelines, subdivision F; Section 81-1, Acute oral Toxicity (Sept 1985)
Qualifier:
according to
Guideline:
other: TSCA: Section 798.1175 (Sept 1985)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
february 24, 1987
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): PEMP (Pentaerythritol Tetrakis (3-Mercaptopropionate))
- Substance type: Organic
- Physical state: Clear liquid
- Density 1.29 g/ml
- No correction for purity applied
Specific details on test material used for the study:
The test was performed with PEMP product, the registered substance.

Test animals

Species:
rat
Strain:
other: CD (Sprague-Dawley derived)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles river Breeding laboratories, Inc., Wilmington, Massachusetts 01887
- Age at study initiation: Appr. 9-12 weeks
- Weight at study initiation: 273-326 g (males); 236-270 g (females)
- Fasting period before study: yes, o/n prior to dosing (appr. 18 hours)
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet: ad libitum, Purina Laboratory Chow
- Water: ad libitum, tap water
- Acclimation period: at least 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no information, monitored and recorded twice daily
- Humidity (%): no information, monitored and recorded twice daily
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: April 4, 1990 To: April 26, 1990

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Maximum dose volume applied: 1.1 mL/kg
Doses:
350, 500, 700, 1000 and 1400 mg/kg bw
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: Twice daily (viability check) and appr. 1, 2 and 4 hours after dosing and daily thereafter (clinical signs)
- Frequency of weighing: prior to fasting, just prior to dosing, day 7 and day 14 (any animal which did not survive for 14 days were weighed at the time of death or at the time that they were found dead)
- Necropsy of survivors performed: yes (all animals except animals used in dose-range finder)
Statistics:
The LD50 was calculated following the method described by Litchfield and Wilcoxon: "A simplified methods of evaluating dose- effect experiments", J. Pharma.Exp. Ther. 96: 99-113 (1949).

Results and discussion

Preliminary study:
No mortality was seen up to 500 mg/kg bw. At 1000 mg/kg bw (given with corn oil as vehicle), one animal died. At 1000 mg/kg bw (without vehicle), also one animal died. All animals died at 2500 and 5000 mg/kg bw.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 700 - <= 1 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 085 mg/kg bw
Based on:
test mat.
95% CL:
>= 883 - <= 1 333
Remarks on result:
other: Calculated LD50
Sex:
female
Dose descriptor:
LD50
Effect level:
908 mg/kg bw
Based on:
test mat.
95% CL:
>= 744 - <= 1 109
Remarks on result:
other: Calculated LD50
Sex:
male/female
Dose descriptor:
LD50
Effect level:
993 mg/kg bw
Based on:
test mat.
95% CL:
>= 863 - <= 1 141
Remarks on result:
other: Calculated LD50
Mortality:
No males died up to 700 mg/ kg bw. One female died at 700 mg/kg bw (at 4 hours post-dose). At 1000 mg/kg bw, 2/5 males died and 3/5 females (at 4 and 5 (males),6, 22 and 22 hours (females) post-dose). At 1400 mg/kg bw, 4/5 males and all females died (at 6 (2 males) and 22 (2 males) hours post-dose; females died after 2 hours (2 females), 6 hours (2 females) and 22 hours post-dose.
Clinical signs:
Nasal and oral discharge, fecal staining, abdominal griping and hypoactivity were noted in most groups at the day of dosing. The number of animals affected was dose-related. Additionally, for some animals convulsions, hyperpnea, ocular discharge and urinary staining were observed. Several animals had decreased food intake on the day of dosing (for one female dosed at 1000 mg/ kg bw, this continued until day 9).
After day 9, no further clinical signs were noted in the surviving animals.
Body weight:
The average weight increase did not change for males exposed up to and including 700 mg/kg bw. At higher doses, the body weight gain decreased. For females, the average body weight gain was similar for females exposed to 350 and 500 mg/ kg bw. The surviving anmals at higher doses showed decreased body weight gain.
Gross pathology:
Gross pathology revealed substance-related changes in the lungs (at 700 mg/kg bw discoloration of the lung was seen in female that was found dead; at higher doses red foci in the lung were seen (one male and one female at 1000 mg/kg bw) and discoloration of the lungs (males and females at 1000 and 1400 mg/kg bw). Furthermore, abnormalities in the gastrointestinal tract were found. In animals exposed to 1000 or 1400 mg/kg bw that were found dead, a yellow fluid was found in the intestines. One male in the group dosed at 1400 mg/ kg bw had red fluid in the intestine. Another male in this group had a thickened stomach wall, and a female at this dose had yellow fluid in the stomach.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study with PEMP conducted conform OECD guideline 401, an LD50 of 908 mg/kg bw was found.
Executive summary:

In an oral toxicity study performed in general conformance with OECD guideline 401, PEMP was dosed to male and female rats (5/ sex/ dose) at 350, 500, 700, 1000 and 1400 mg/kg bw. No males died up to 700 mg/kg bw, one female died at 700 mg/kg bw. At 1000 mg/kg bw, 2/5 males died and 3/5 females and at 1400 mg/kg bw, 4/5 males and all females died. All rats died within 24 hours of dosing. Several clinical signs were noted, including nasal and oral discharge, fecal staining, abdominal griping and hypoactivity at the day of dosing. The number of animals affected was dose-related. Additionally, for some animals convulsions, hyperpnea, ocular discharge and urinary staining were observed. Several animals had decreased food intake on the day of dosing (for one female dosed at 1000 mg/kg bw, this continued until day 9). At necropsy, substance-related changes in the lungs at 700 mg/kg bw and above were seen (discoloration and/or red foci in the lung). Furthermore, abnormalities in the gastrointestinal tract were found. In animals exposed to 1000 or 1400 mg/kg bw that were found dead, a yellow fluid was found in the intestines. One male in the group dosed at 1400 mg/kg bw had red fluid in the intestine. Another male in this group had a thickened stomach wall, and a female at this dose had yellow fluid in the stomach.

Based on these data, the oral LD50 for PEMP was determined to be 908 mg/kg bw, the substance is classified for oral toxicity in category 4 according to Regulation (EC) 1272/2008.