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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 September 30, 1980 to March 17, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the equivalent of standard guidelines.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Method: 40 CFR Part 163.81-1 (Environmental Protection Agency Pesticide Programs. Proposed Guidelines for Registering Pesticides in the U.S.; Hazard Evaluation: Humans and Domestic Animals. Acute Oral Toxicity Study)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: Young adults
- Weight at study initiation: Males: 247-335 g and females: 213-254 g
- Fasting period before study: Overnight
- Housing: Six animals/cage in suspended, stainless steel with wire-mesh bottoms
- Diet (e.g. ad libitum): Purina Laboratory Rodent Diet, ad libitum
- Water (e.g. ad libitum): Municipal water, ad libitum
- Acclimation period: 14-28 d


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64-78 °F
- Photoperiod (h dark / h light): 12 h dark / 12 h light
Route of administration:
oral: gavage
Vehicle:
other: 1 % methylcellulose
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 0.04 - 4.2 mL/kg
Doses:
Range-finding test: 50, 100, 500, 1,000, 2,000 or 5,000 mg/kg bw
LD50 determination: 250, 350, 500, 700, 1,000, 1,400 or 2,000 mg/kg bw
No. of animals per sex per dose:
Range-finding screen: 5/sex (at 5,000 mg/kg bw); one/sex/dose (at other doses)
LD50 determination: 5/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations: Pharmacological and toxicological signs were observed approximately 1, 2, and 4 h after dosing and daily thereafter for 14 d; weighing done at pre-fast, post-fast (just prior to dosing), day 7 and 14 or at terminal sacrifice
- Necropsy of survivors performed: Yes; surviving animals were killed by carbon dioxide inhalation
Statistics:
Mortality data were analyzed by probit analysis method.
Preliminary study:
Not applicable
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
620 mg/kg bw
95% CL:
> 480 - < 760
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
420 mg/kg bw
95% CL:
> 340 - < 500
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
540 mg/kg bw
95% CL:
> 440 - < 640
Mortality:
Range-finding agent:
- 0/2, 0/2, 0/1, 1/2, 2/2 and 10/10 animals died at 50, 100, 500, 1,000, 2,000 and 5,000 mg/kg bw, respectively
LD50 determination test:
- 0/9, 2/10, 4/10, 9/10, 8/9, 10/10 and 8/8 animals died at 250, 350, 500, 700, 1,000, 1,400 and 2,000 mg/kg, respectively
Clinical signs:
- Decreased activity, dyspnea, soft stool, fecal staining, oral discharge, hypopnea and rales were observed at all dose levels
- No unusual clinical signs were observed in the surviving animals
Body weight:
Most surviving male animals gained weight between days 7-14. Several surviving females lost weight after 7 d, but all exhibited gains between days 7 and 14. No dose-related differences were apparent.
Gross pathology:
Examinations of animals which died revealed a variety of changes, primarily in the lungs and gastrointestinal tract; most of these were considered to represent post-mortem changes.
Other findings:
None

None

Conclusions:
Under the conditions of the study, the acute oral LD50 of the substance in male and female rats was calculated to be 620 (480-760) and 420 (340-500) mg/kg bw. The combined LD50 for male/female rats was calculated to be 540 (440-640) mg/kg bw.
Executive summary:

A study was conducted to assess the single dose toxicity of C-171 in Sprague-Dawley rats using a method equivalent or similar to OECD Guideline 401. 

Groups of 10 Sprague-Dawley rats (5/sex/dose) received a single oral (gavage) dose of 250, 350, 500, 700, 1,000, 1,400 or 2,000 mg/kg bw. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 day observation period.

Mortality was 0/9 at 250 mg/kg bw, 2/10 at 350 mg/kg bw, 4/10 at 500 mg/kg bw, 9/10 at 700 mg/kg bw, 8/9 at 1,000 mg/kg bw, 10/10 at 1,400 mg/kg bw and 8/8 at 2,000 mg/kg bw. All surviving animals showed gains in body weight between Days 7-14. Necropsy of animals which died prior to termination revealed a variety of changes, primarily in the lungs and gastrointestinal tract, most of which were considered to represent post-mortem changes.

Clinical signs noted at all dose levels were decreased activity, dyspnea, soft stool, fecal staining, oral discharge, hypopnea and rales. No unusual clinical signs were observed in the surviving animals.

In conclusion, under the conditions of the study, the acute oral LD50 of the substance in male/female rats was calculated to be 620 (480 -760) and 420 (340 -500) mg/kg bw. The combined LD50 for male/female rats was calculated to be 540 (440 -640) mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
540 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
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:
From September 25, 1980 to October 28, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the equivalent of standard guidelines.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Method: 40 CFR Part 163.81-2 (Environmental Protection Agency, Pesticide Programs. Proposed Guidelines for Registering Pesticides in the U.S.; Hazard Evaluation: Humans and Domestic Animals. Acute Dermal Toxicity Study)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Penn Dutch Laboratory Animals Denver, Pennsylvania
- Age at study initiation: Young adults
- Weight at study initiation: Males: 2.2-2.8 kg and females: 2.5-2.9 kg
- Housing: Individually in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): Municipal water, ad libitum
- Acclimation period: 19 d


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-66 °F
- Photoperiod (h dark / h light): 12 h dark / 12 h light
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- % coverage: 10 % of the body surface area
- Type of wrap if used: Test material applied directly, covered by gauze and then wrapped with an impervious plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test site wiped free of excess test material
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.7 mL/kg
- Concentration (if solution): 2,000 mg/kg
Duration of exposure:
24 h
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
Six males and four females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations: Animals were observed twice daily for viability check; pharmacological/toxicological signs were observed at 1, 2 and 4 h after dosing and daily thereafter for 14 d; weighed at pre-dose (at the time of clipping), day of dosing , days 7 and 14 or at terminal sacrifice
- Necropsy of survivors performed: Yes; surviving animals were killed by intravenous overdose of sodium pentobarbital
- Other examinations performed: Local irritation reactions were observed 30 min after removal of test material
Statistics:
No data
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
2 000 mg/kg bw
Mortality:
All animals survived throughout the study period
Clinical signs:
- Nasal and/or oral or ocular discharge were observed in several animals during the 14-d post-dose period
- Fecal staining of the abdomen was observed in one animal at 24 h
Body weight:
All animals showed body weight gain except one male and one female
Gross pathology:
Necropsy revealed abnormalities like small or pale spleen; red foci in adrenals; raised, yellow and hard seminal vesicles; tan lungs; stomach or small intestines extremely distended with gas.
Other findings:
- Decreased food consumption was observed in one animal

Local irritation reactions at application site:
- Well-defined to severe erythema with moderate or severe edema at 24 h
- Two animals exhibited eschar at the dosing site at terminal necropsy

None

Conclusions:
Under the conditions of the study, the acute dermal LD50 of C-171 in male/female rabbits was > 2,000 mg/kg bw. The discriminating dose is 2,000 mg/kg bw.
Executive summary:

A study was conducted to assess the acute dermal toxicity of C-171 in New Zealand White rabbits using the method equivalent or similar to OECD Guideline 402.

A group of 6 male and 4 female New Zealand White rabbits received a single dermal application of 2,000 mg/kg bw at a dose volume of 1.7 mL/kg to a shaved area of the back representing 10 % of the total body surface area. The application was occluded and exposure was for 24 h. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 days observation period.

No mortality occured at 2,000 mg/kg bw. All animals, except one male and one female, showed body weight gain during the study.

Clinical signs noted in several animals were nasal and/or oral or ocular discharge. Decreased food consumption and fecal staining of the abdomen were observed in one animal at 24 h. Well-defined to severe erythema with moderate or severe edema were observed at the application site at 24 h. Two animals exhibited eschar at the dosing site at terminal necropsy. Necropsy revealed abnormalities like small or pale spleen; red foci in adrenals; raised, yellow and hard seminal vesicles; tan lungs; stomach or small intestines extremely distended with gas.

 

In conclusion, under the conditions of the study, the acute dermal LD50 of C-171 in male/female rabbits was > 2,000 mg/kg bw. The discriminating dose is 2,000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
More reliable of two studies.

Additional information

Oral

A study was conducted to assess the single dose toxicity of C-171 / SN-2916 in Sprague-Dawley rats using a method equivalent or similar to OECD Guideline 401. Groups of 10 Sprague-Dawley rats (5/sex/dose) received a single oral (gavage) dose of250, 350, 500, 700, 1,000, 1,400 or 2,000 mg/kg bw.Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 day observation period. Mortality was 0/9 at 250 mg/kg bw, 2/10 at 350 mg/kg bw, 4/10 at 500 mg/kg bw, 9/10 at 700 mg/kg bw, 8/9 at 1,000 mg/kg bw, 10/10 at 1,400 mg/kg bw and 8/8 at 2,000 mg/kg bw. All surviving animals showed gains in body weight between Days 7-14. Necropsy of animals which died prior to termination revealed a variety of changes, primarily in the lungs and gastrointestinal tract, most of which were considered to represent post-mortem changes. Clinical signs noted at all dose levels were decreased activity, dyspnea, soft stool, fecal staining, oral discharge, hypopnea and rales. No unusual clinical signs were observed in the surviving animals. In conclusion, under the conditions of the study, the acute oral LD50 of the substance in male/female rats was calculated to be 620 (480 -760) and 420 (340 -500) mg/kg bw. The combined LD50 for male/female rats was calculated to be 540 (440 -640) mg/kg bw (Auletta, 1981a).

A study was conducted to assess the single dose toxicity of C-78 / SN-204 in Sprague-Dawley rats using a method equivalent or similar to OECD Guideline 401. Groups of 10 Sprague-Dawley rats received a single oral (gavage) dose of 400, 500, 1,000, 3,000 and 5,000 mg/kg bw. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 day observation period. Mortality at dose levels of 400, 500, 1,000, 3,000 and 5,000 mg/kg bw was 10, 30, 50, 100 and 100%, respectively. All surviving animals showed gains in body weight over the study period. Abnormalities at necropsy consisted of gas and/or fluid in the stomach/intestine; enlargement of the stomach; compound in stomach; discoloration of liver (dark), intestines (reddened), stomach lining (reddened) and red material in the stomach/intestines. Clinical signs noted were soft feces and slight to marked depression (at 500, 1,000, 3,000 and 5,000 mg/kg bw); rough hair coat (at 1,000, 3,000 and 5,000 mg/kg bw); urine stains (at 500, 1,000 and 3,000 mg/kg bw) and ataxia (at 3,000 mg/kg bw). In conclusion, under the conditions of the study, the acute oral LD50 of the test substance in male and female rats was calculated to be 1,156 and 608 mg/kg bw, respectively. The combined LD50 for both male and female rats was calculated to be 837 mg/kg bw (Wolfe, 1979).

A study was conducted to assess the single dose toxicity of SN-1716 in Sprague-Dawley rats using a method equivalent or similar to OECD Guideline 401. Groups of 4 Sprague-Dawley rats received a single oral (gavage) dose of 900, 1,350, 2,025, 3,038, 4,556 or 15,380 mg/kg bw . Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 day observation period. Mortality at dose levels of 900, 1,350 and 2,025-15,380 mg/kg bw was 0, 50 and 100 % respectively. All surviving animals showed gains in body weight during the study period. Abnormalities at necropsy consisted of gastrointestinal hemorrhages and purple, discolored testes. Clinical signs noted were hypoactivity, salivation, ptosis and diarrhea (at all dose levels), muscular weakness and labored breathing (at 3,038, 4,556 and 15,380 mg/kg bw), prostration (at 15,380 mg/kg bw) and diuresis (at 900, 1,350 and 2,025 mg/kg bw). Under the conditions of the study, the acute oral LD50 of the test substance in male/female rats was calculated to be 1,350 (± 158.4) mg/kg bw (Trzyna and Paa, 1976).

Dermal

A study was conducted to assess the acute dermal toxicity of C-171 in New Zealand White rabbits using the method equivalent or similar to OECD Guideline 402. A group of 6 male and 4 female New Zealand White rabbits received a single dermal application of 2,000 mg/kg bw at a dose volume of 1.7 mL/kg to a shaved area of the back representing 10 % of the total body surface area. The application was occluded and exposure was for 24 h. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 days observation period. No mortality occured at 2,000 mg/kg bw. All animals, except one male and one female, showed body weight gain during the study. Clinical signs noted in several animals were nasal and/or oral or ocular discharge. Decreased food consumption and fecal staining of the abdomen were observed in one animal at 24 h. Well-defined to severe erythema with moderate or severe edema were observed at the application site at 24 h. Two animals exhibited eschar at the dosing site at terminal necropsy. Necropsy revealed abnormalities like small or pale spleen; red foci in adrenals; raised, yellow and hard seminal vesicles; tan lungs; stomach or small intestines extremely distended with gas. In conclusion, under the conditions of the study, the acute dermal LD50 of C-171 in male/female rabbits was > 2,000 mg/kg bw (Auletta, 1980a).

A study was conducted to assess the acute dermal toxicity of SN-1716 in New Zealand White rabbits using the method equivalent or similar to OECD Guideline 402 (Acute Dermal Toxicity). A group of New Zealand White rabbits received a single dermal application of 2,000 mg/kg bw to a shaved area of the back representing 30 % of the total body surface area. The application was occluded and exposure lasted 24 h. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 day observation period. Mortality was 1 / 4at 2,000 mg/kg bw. All surviving animals showed gains in during the study. Necropsy of the animals revealed a variety of changes, primarily in the lungs and gastrointestinal tract; most of these were considered to represent post-mortem changes. Clinical signs noted were decreased activity, dyspnea, soft stool, fecal staining, oral discharge, hypopnea and rales. No unusual clinical signs were observed in the surviving animals. Advanced post-mortem autolysis was observed at necropsy of the one animal that died before the end of the study. The substance was severely irritating to the skin of the rabbit. Skin changes at 24 h were characterized by red, well-defined to beet red erythema, severe edema and second degree burns. Pale-red to red, well-defined erythema, second degree burns, escharosis, wrinkling and fissuring were observed on Day 7. Escharosis was noted on Day 14. In conclusion, under the conditions of the study, the acute dermal LD50 of the test substance in male/female rabbits was > 2,000 mg/kg bw (Trzyna and Paa, 1976).

Justification for selection of acute toxicity – oral endpoint

Lowest LD50 of three studies.

Justification for classification or non-classification

Based on studies conducted in rats, PETIA appears to be moderately toxic when administered via the oral route, with LD50 values ranging between 540 and 1,350 mg/kg bw. It therefore qualifies for classification as Acute Tox. 4 - H302 (Harmful if swallowed) according to EU CLP (EC 1272/2008) criteria.

PETIA has low vapour pressure so that normal processing and use conditions will not generate inhalation exposure. Appropriate risk management measures such as closed systems, exhaust ventilation and/or wearing of respirators are implemented to control exposure. Uses creating aerosols or vapours (e.g. spraying, elevated temperature/pressure), are not covered in this registration. Acute inhalation exposure is therefore not expected to pose an issue for human health.

Toxicity via the dermal route is low (dermal LD50 (rabbit) > 2,000 mg/kg bw) so that no classification for this endpoint is warranted.