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Description of key information

In an acute oral toxicity study with PEMP conducted conform OECD guideline 401, the LD50 was calculated as 1085 mg/kg bw for male, 908 mg/kg bw for female and 993 mg/kg bw for male/female. An acute dermal toxicity test was conducted according to OECD/ EC guidelines and GLP principles with PEMP. Based on the results it is concluded that the dermal LD50 of this test substance is > 2000 mg/kg bw. Both studies have Klimisch reliability 1.

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:
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.
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
Specific details on test material used for the study:
The test was performed with PEMP product, the registered substance.
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
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).
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
908 mg/kg bw
Quality of whole database:
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 (Klimisch 1).

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:
25 June - 9 July 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of Inspection 17 March 1992
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
The test was performed with PEMP product, the registered substance.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Age at study initiation: appr. 10-14 weeks
- Weight at study initiation: 230-241g (males); 209-227g (females)
- Fasting period before study: No
- Housing: In suspended polypropylene cages, individually during 24-hour exposure period and group-housed with 5 animals per cage thereafter
- Diet: Ad libitum, Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.
- Water: Ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 47-75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 June 1992 To: 9 July 1992
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm * 4 cm
- % coverage: appr. 10% of total body surface area
- Type of wrap if used: surgical gauze held in place by a piece of self-adhesive bandage (HYPERTIE and BLENDERM)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no, exposure area was wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2000 mg/ kg bw
Duration of exposure:
24 hours
Doses:
2000 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: 0.5, 1,2 and 4 hours after dosing and subsequently once daily
- Frequency of weighing: prior to application on day 0 and on days 7 and 14
- Necropsy of survivors performed: yes (gross macroscopy)
- Other examinations performed: any adverse dermal reactions were recorded
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs were noted during the study.
Body weight:
All animals showed expected body weight gain during the study.
Gross pathology:
The macroscopic observations did not reveal any abnormalities.
Other findings:
Adverse skin reactions were noted for three females: haemorrhage of the dermal capillaries, moderate erythema, keratolysis (glossy skin), small superficial scattered scabs and desquamation. The skin of these treated animals appeared normal 7 days after treatment.
Interpretation of results:
GHS criteria not met
Conclusions:
An acute dermal toxicity test was conducted according to OECD/ EC guidelines and GLP principles with PEMP. Based on the results it is concluded that the dermal LD50 of this test substance is > 2000 mg/kg bw.
Executive summary:

An acute dermal toxicity test was conducted according to OECD/ EC guidelines and GLP principles with PEMP. Five male and five female rats were semi-occlusively exposed for 24 hours to 2000 mg/kg bw. No mortality occurred, no clinical signs were noted. Three females were found to have adverse skin reactions, including haemorrhage of the dermal capillaries, moderate erythema, keratolysis (glossy skin), small superficial scattered scabs and desquamation. The skin of these treated animals appeared normal 7 days after treatment.

Based on these data, the dermal LD50 for PEMP was determined to exceed 2000 mg/kg bw, therefore the substance is not classified for dermal toxicity according to Regulation (EC) 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study was performed according to OECD/EC guidelines and GLP principles.

Additional information

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 calculated to be1085mg/kg bwfor maleand 908 mg/kg bw for female.

An acute dermal toxicity test was conducted according to OECD/ EC guidelines and GLP principles with PEMP. Five male and five female rats were semi-occlusively exposed for 24 hours to 2000 mg/kg bw. No mortality occurred, no clinical signs were noted. Three females were found to have adverse skin reactions, including haemorrhage of the dermal capillaries, moderate erythema, keratolysis (glossy skin), small superficial scattered scabs and desquamation. The skin of these treated animals appeared normal 7 days after treatment.

Justification for classification or non-classification

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.

The dermal LD50 for PEMP was determined to exceed 2000 mg/kg bw, therefore the substance is not classified for dermal toxicity according to Regulation (EC) 1272/2008.