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Description of key information

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:
From 08 to 23 March 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to EU guideline 84/449/EC in compliance with GLP. Analytical certificate not included in study report.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
other: EU guideline 84/449/EC of 19/09/1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchem, Germany
- Age at study initiation: 9 (males) or 10 (females) weeks
- Weight at study initiation: 172 (males) or 173 (females) g
- Fasting period before study: 16 to 4 h before test begin
- Housing: Makrolon Type III cages
- Diet (e.g. ad libitum): Fixed formula standard diet Altromin 1324 pellets (Altromin GmbH)
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw
Doses:
1,000 (only females), 2,000, 3,100 and 5,000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Several times on the day of dosing then twice daily until test end: type, onset, duration and intensity of symptoms and mortality. Predosing, after one week and at test end: bodyweight
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
According to Rosiello AP et al. (1977), J. Tox. Environ. Health 3:797, modified by Pauluhn J (Bayer AG, report no. 11835, 1983). Based on maximum likelihood method of Bliss CI (1938), Q. J. Pharm. Pharmacol. 11:92.
Sex:
male
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

As of 3,100 (males) and 2,000 (females) mg/kg bw, observed symptoms included poor general condition, rough fur, sedation, unconsciousness, side or stomach position, paralysis-like effects in the posterior extremities. High gait was seen in males at 5,000 mg/kg bw and females at 2,000 and 5,000 mg/kg bw. Bloody nose and weight loss were observed in females at 2,000 mg/kg bw. In one female at 3,100 mg/kg bw, there was shortness of breath.

In males at 5,000 mg/kg bw and females as of 3,100 mg/kg bw which died before test end, gross macroscopical examination revealed damaged mucous membrane of the stomach, redenned stomach fundus, as well as redenned and swollen gastro-intestinal tract. One male and 2 females at 5,000 mg/kg bw also displayed redenned lungs.

There were no symptoms at 2,000 (males) and 1,000 (females) mg/kg bw.

Conclusions:
Under the conditions of the study, the acute oral LD50 of the substance was 5,000 mg/kg bw for males and > 2,000 mg/kg bw for females.
Executive summary:

A study was conducted to determine the acute oral toxicity of NPEO to rat in accordance with EU Guideline 84/449/EC of 19/09/1984. Male and female Wistar rats received the test substance diluted in polyethylene glycol via gavage at doses of 1,000 (females only), 2,000, 3,100 and 5,000 mg/kg bw. Mortality and clinical signs were recorded throughout the study. Gross macroscopy was conducted at the end of the test period. As of 3,100 (males) and 2,000 (females) mg/kg bw, symptoms included poor general condition, rough fur, sedation, unconsciousness, side or stomach position, paralysis-like effects in the posterior extremities. High gait was seen in males at 5,000 mg/kg bw and females at 2,000 and 5,000 mg/kg bw. Bloody nose and weight loss were observed in females at 2,000 mg/kg bw. In one female at 3,100 mg/kg bw, there was shortness of breath. In males at 5,000 mg/kg bw and females as of 3,100 mg/kg bw which died before test end, gross macroscopical examination revealed damaged mucous membrane of the stomach, redenned stomach fundus, as well as redenned and swollen gastro-intestinal tract. One male and 2 females at 5,000 mg/kg bw also displayed redenned lungs. Under the conditions of the study, the acute oral LD50 of the substance was 5,000 mg/kg bw for males and > 2,000 mg/kg bw for females (Ivens-Kohl I, 1988).

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary literature source (documentation insufficient for assessment)
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
No data
GLP compliance:
not specified
Test type:
other: no data
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data
Duration of exposure:
No data
Doses:
No data
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data
Statistics:
No data
Preliminary study:
No data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No data
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
No data

No data

Conclusions:
According to the test results, the dermal LC50 for NPE-4 was determined to be greater than 2,000 mg/kg bw.
Executive summary:

A study was conducted to evaluate the acute dermal toxicity of a commercial formulation of NPE-4 to rabbit. Under the study conditions, the dermal LD50 was > 2,000 mg/kg bw (Talmage SS, 1994).

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Oral

A study was conducted to determine the acute oral toxicity of NPEO to rat in accordance with EU Guideline 84/449/EC of 19/09/1984. Male and female Wistar rats received the test substance diluted in polyethylene glycol via gavage at doses of 1,000 (females only), 2,000, 3,100 and 5,000 mg/kg bw. Mortality and clinical signs were recorded throughout the study. Gross macroscopy was conducted at the end of the test period. As of 3,100 (males) and 2,000 (females) mg/kg bw, symptoms included poor general condition, rough fur, sedation, unconsciousness, side or stomach position, paralysis-like effects in the posterior extremities. High gait was seen in males at 5,000 mg/kg bw and females at 2,000 and 5,000 mg/kg bw. Bloody nose and weight loss were observed in females at 2,000 mg/kg bw. In one female at 3,100 mg/kg bw, there was shortness of breath. In males at 5,000 mg/kg bw and females as of 3,100 mg/kg bw which died before test end, gross macroscopical examination revealed damaged mucous membrane of the stomach, redenned stomach fundus, as well as redenned and swollen gastro-intestinal tract. One male and 2 females at 5,000 mg/kg bw also displayed redenned lungs. Under the conditions of the study, the acute oral LD50 of the substance was 5,000 mg/kg bw for males and > 2,000 mg/kg bw for females (Ivens-Kohl I, 1988).

A study was conducted to evaluate the acute oral toxicity of NPEO in rats. Six male Charles River CD rats were exposed to the substance at a single oral dose (15,000 mg/kg bw) selected on the basis of a range finding study conducted at dose levels of 500, 1,000, 3,000, 6,000, 9,000 and 12,000 mg/kg bw. The animals were observed for the duration of 14 d. No clinical signs or mortality was observed at any dose level. The oral LD50 in rats was therefore determined to be greater than 15,000 mg/kg bw (Cuthbert JA, 1975).

A study was conducted to determine the acute oral toxicity of NPEO to rat following an experimental procedure based on OECD Guideline 401. Male and female rats were exposed to the test substance at 0, 7,500, 9,400, 11,800 and 15,000 mg/kg bw. Mortality occurred at 7,500 mg/kg bw and above within 22 h of dosing. Clinical signs observed shortly after dosing in all rats were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, pallor of the extremities and increased salivation. These signs were accompanied by decreased respiratory rate amongst rats of all groups, diarrhoea and comatose-like condition at 9,400 mg/kg bw and above. Recovery as judged by external appearance and behaviour was apparently complete by Day 10. In the animals that died, bodyweight losses were recorded, as well as congestion or haemorrhage of the lungs and pallor of the kidneys. In surviving animals, bodyweight appeared normal and there were no findings at terminal autopsy. Under the conditions of the study, the combied DL50 (males and females) was estimated to be 8,400 mg/kg bw.

Dermal

A study was conducted to evaluate the acute dermal toxicity of NPE-4 (no information on purity) to rabbit. The undiluted test item was applied once under occlusion to the shaved abraded skin of five female rabbits in the dosage range of 1.0 - 6.6 mL/kg bw. The patches were removed at 24 h, the exposed sites rinsed and the animals observed for 14 days. Under the study conditions, the dermal LD50 was determined to be 2.5 mL/kg bw. Erythema and necrosis of the skin was observed at various doses. Lung congestion and hemorrhages was seen in dead animals (CIR, 1983).

Studies were conducted to evaluate the acute dermal toxicity of commercial formulations of NPE-4 to rabbit. Under the study conditions, the dermal LD50 were > 3,000 and > 2,000 mg/kg bw, respectively (Talmage SS, 1994). The same authors report testing on NP(no information on purity), with a dermal LD50 in rabbit of 2,031 mg/kg bw.

Justification for classification or non-classification

Based on available data for NPEO, NPE-4 and NP, low acute oral and dermal toxicity is expected for NPEO, with LD50 values >2,000 mg/kg bw for both exposure routes. The substance therefore does not require classification for these endpoints according to CLP (EC 1272/2008) and DSD (67/548/EEC) criteria.