Pyridine, alkyl derivs.

Endpoint summary

Description of key information

Several acute toxicity studies were carried out, with key studies available for all relevant routes. Acute oral toxicity studies were carried out with Pyridine, alkyl derivs. Acute inhalation and acute dermal toxicity studies were carried out with 5-ethyl-2-methylpyridine (MEP, CAS no.: 104-90-5, EC no.: 203-250-0). The read-across between the UVCB substance and the model constituent is justified.
In a study similar or equivalent to EU Method B.1 and OECD Guideline 401 (Acute toxicity oral) the LD50 oral was determined to be 1.35 mL/kg bw (1350 mg/kg bw). In a study similar or equivalent to EU Method B.2 and OECD Guideline 403 (Acute Inhalation Toxicity) the LC50 inhalation was determined 2.67 mg/L (2670 mg/m3). In a study similar or equivalent to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity) the LD50 dermal was determined 1000 mg/kg bw.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study.

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

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
- Weight at study initiation: 190 - 220 g (males) and 140 - 160 g (females)
- Fasting period before study: Overnight fast (for 18 - 20 hours before treatment)
- Housing: Solid floor polypropylene boxes furnished with softwood sawdust
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Not less than 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 10

IN-LIFE DATES:
- July 1977

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
- All animals were treated with neat material

Doses:

A single oral dose of test material, based on the fasted body weight of the animals at the time of treatment, was administered by gavage using a metal stomach tube. The animals were then returned to their cages for observation.
Range finding study: 1.0, 3.0 mL/kg bw
Main study: 1.0, 1.5, 2.0, 2.5 and 5.0 mL/kg bw

No. of animals per sex per dose:

Range finding study: 2 male/2 female animals per dose
Main study: 5 male/5 female animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for overt toxicity at 0.25, 1, 2 and 4 hours after treatment and subsequently once daily for 14 days, body weights of survivors were recorded at 7 and 14 days after treatment.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, gross necropsy

Statistics:

Litchfield and Wilcoxon (A simplified method for the evaluation of dose effect experiments, J. Pharm. Exp. Therap. 96, 99, (1949).

Preliminary study:

Two groups each of 4 fasted rats (2 males, 2 females) were dosed with 1.0 and 3.0 mL/kg bw. Mortalities were recorded at daily intervals for the following 7 days.

Sex:

male

Dose descriptor:

LD50

Effect level:

1.55 mL/kg bw

Based on:

test mat.

95% CL:

1.4 - 1.72

Sex:

female

Dose descriptor:

LD50

Effect level:

1.35 mL/kg bw

Based on:

test mat.

95% CL:

1.1 - 1.66

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1.42 mL/kg bw

Based on:

test mat.

95% CL:

1.19 - 1.69

Mortality:

For determination of the formal LD50 twenty-six mortalities occurred during the study, 23 of which were within 24 hours of treatment. One mortality of a high dose male was observed within 4 hours and of 1 high dose female 48 hours after treatment. For one male rat dosed with 1.5 mL/kg bw mortality was noted 4 days after treatment.

Clinical signs:

All animals appeared subdued and lethargic within 15 minutes of treatment; this behaviour was not apparent at 24 hours. All survivors throughout dose groups showed dull staring coats, laboured respiration and hunched posture within 24 hours of treatment. All rats were asymptomatic at 72 hours.

Body weight:

All male survivors showed normal gains in body weight throughout the 14 day observation period. The low dose female survivors showed small body weight gains during the 14 day observation period. The female survivors dosed with 1.5 mL/kg bw showed loss in body weight at the 7 day observation and a very small increase in body weight at 14 days.

Gross pathology:

Gross necropsy of all animals (mortalities and survivors) showed no detectable abnormalities.

Other findings:

None.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results obtained in this acute toxicity study the LD50 value obtained for males was 1.55 mL/kg bw (1.40 - 1. 72) for females 1.35 mL/kg bw (1.10 - 1. 66) and for males/females 1.42 mL/kg bw (1.19 - 1.69).

Executive summary:

A study was carried out equivalent or similar to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity). Following a dose-range finding study, 5 groups of 10 rats (5 male, 5 female) of the Sprague Dawley strain were treated with a single oral dose of test item within the dose range 1.0 - 5.0 mL/kg bw. A log dose-mortality curve was constructed and the acute oral LD50 and 95 % fiducial limits calculated by the method of Litchfield and Wilcoxon. The LD50 value obtained for males was 1.55 mL/kg bw (1.40 - 1. 72) for females 1.35 mL/kg bw (1.10 - 1. 66) and for males/females 1.42 mL/kg bw (1.19 - 1.69).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 350 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2 670 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Additional information

Key study: Acute toxicity – oral

A study was carried out equivalent or similar to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity). Following a dose-range finding study, 5 groups of 10 rats (5 male, 5 female) of the Sprague Dawley strain were treated with a single oral dose of test item within the dose range 1.0 - 5.0 mL/kg bw. A log dose-mortality curve was constructed and the acute oral LD50 and 95 % fiducial limits calculated by the method of Litchfield and Wilcoxon. The LD50 value obtained for males was 1.55 mL/kg bw (1.40 - 1. 72) for females 1.35 mL/kg bw (1.10 - 1. 66) and for males/females 1.42 mL/kg bw (1.19 - 1.69).

Supporting study 1: Acute toxicity – oral

A study was carried out equivalent or similar to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity). A total of 7 groups of 10 young adult Albino rats (5 male, 5 female) were treated with a single oral dose of test item within the dose range 1.0 - 4.0 mL/kg bw. Based on the results obtained in this acute toxicity study the LD50 for males obtained was 1.94 mL/kg bw (95 % CL 1.67 - 2.24) and for females 2.46 mL/kg bw day (95 % CL 2.0 - 3.03).

Supporting study 2: Acute toxicity – oral

A study was carried out equivalent or similar to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity). A total of 8 groups of 10 young adult Albino rats (5 male, 5 female) were treated with a single oral dose of test item within the dose range 1.0 - 8.0 mL/kg bw. Based on the results obtained in this acute toxicity study the LD50 for males obtained was 3.25 mL/kg bw (95 % CL 2.1 - 5.0) and for females 3.1 mL/kg bw day (95 % CL 2.7 - 3.6).

Supporting study 3: Acute toxicity – oral

A study was carried out equivalent or similar to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity). A total of 5 groups of 10 Wistar rats (5 male, 5 female) were treated with a single oral dose of test item within the dose range 1.0 – 3.2 mL/kg bw. Based on the results obtained in this acute toxicity study the LD50 for males and females was 1.67 mL/kg bw day (95 % CL 1.28 - 2.17).

Key study: Acute toxicity – inhalation

Determination of acute inhalation toxicity was carried out with 5-ethyl-2-methylpyridine (MEP, CAS no.: 104-90-5, EC no.: 203-250-0). The read-across between the UVCB substance and the model constituent is justified. A study similar or equivalent to EU Method B.2 and OECD Guideline 403 (Acute Inhalation Toxicity) was carried out. Rats were dosed for 4 hours. An LC50 of 2.67 mg/L was obtained.

Key study: Acute toxicity – dermal

Determination of acute dermal toxicity was carried out with 5-ethyl-2-methylpyridine (MEP, CAS no.: 104-90-5, EC no.: 203-250-0). The read-across between the UVCB substance and the model constituent is justified. A study similar or equivalent to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity) was carried out. Rabbits were administered a single dermal dose. An LD50 of 1000 mg/kg bw was revealed.

Justification for classification or non-classification

Based on the data available the substance is classified and labeled according to Regulation 1272/2008/EEC (CLP) as Acute toxicity category 4, Oral H302 Harmful if swallowed, acute toxicity category 3, Dermal H311 Toxic in contact with skin, acute toxicity category 3, Inhalation H331 Toxic if inhaled and Xn harmful, R20/21/22 Harmful by inhalation, in contact with skin and if swallowed according to Directive 67/548/EEC (DSD).