3-pyridyl dimethylcarbamate

Endpoint summary

Description of key information

GLP guideline study according to OECD 401

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:

1999-02-23 to 1999-08-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 February, 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

- CAS No.: 51581-32-9
- Batch No.: TMFP 304
- Purity: at least 99 %
- Solubility in water: Soluble
- Storage: In the refrigerator, in the dark
- Date of expiry: December 1999
- Appearance: Colorless liquid
- pH: 7.29

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Forschungsinstitut für Versuchstierzucht, A-2325 Himberg
- Age at study initiation: 8 weeks (males) and 12 weeks (females)
- Weight at study initiation: approximately 161 - 164g for males and 256 g for females
- Housing: Single caging
- Diet (e.g. ad libitum): Yes
- Water (e.g. ad libitum): Yes
- Acclimation period: 5 days (females) and 12 days (males)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 49
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL per kg body weight

Doses:

Females: 15, 50, 150 mg / kg bw
Males: 50 mg / kg bw

No. of animals per sex per dose:

5 per dose group. 3 dose groups for females and one for males

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration and then at least once a day for a total of two weeks
- Frequency of weighing: Before administration, 7 days p.a, 14 days p.a., the day of death from animals died between days 1 - 14. Body weight gain was calculated for each week of the study, i.e. between 0 and 7 d p.a., 7 and 14 d p.a.
- Necropsy of survivors performed: yes

Statistics:

Statistical methods including Bias control, LD50 and the upper and lower limits of confidence (95%) were calculated

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

99.4 mg/kg bw

Based on:

test mat.

Mortality:

Females: All animals survived until the scheduled termination of the study at 15 and 50 mg / kg bw. 4 / 5 animals died on the day of administration at 150 mg / kg body weight
Males: All animals survived until the scheduled termination of the study at 50 mg / kg bw

Clinical signs:

- Autonomous nervous effects: Increased salivation in mid and high dosed females
- Central nervous effects: Sedation in females and 4 / 5 males, abnormal posture in two mid dosed and in all high dosed females, tremor in two low dosed females and in all females and males of the other groups, disturbed locomotion in 4 / 5 males, clonic convulsions in 4 / 5 females of the high dosed group and righting reflex catalepsy in all mid and high dosed females and in one male.
- Signs of pain or of reduced well-being: Piloerection in all animals, hunched posture in nearly all animals, sunken flanks in one mid dosed and two high dosed females and chromodakryorrhea in one high dosed female and two males

Body weight:

males and females: Body weights and body weight gain were inconspicuous in all animals

Gross pathology:

No abnormal findings were made post mortem

Other findings:

- Other effects: Dyspnoea in high dosed females, respiratory murmur and oedema of the skull in one high dosed female each, exophthalmus in one high dosed female and in 4 / 5 males and a corneal lesion in one high dosed female.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In this study, the test substance is considered toxic under the UN GHS Criteria "Category III"

Executive summary:

In an acute oral toxicity study, the test item, diluted with deionised water was administered orally to male and female Sprague Dawley rats at a dose volume of 10 mL kg body weight at concentrations of 15, 50 and 150 mg / kg bw for males and 50 mg / kg bw for females. The LD50 for females was determined to be 99.4 mg / kg body weight. The test substance caused effects on the autonomous (e.g. salivation) and the central nervous system and a cardiovascular disorder (oedema). The signs indicate a cholinesterase-inhibiting effect, which is also likely due to the chemical nature of the test substance, but also an anaphylactoid reaction (skull oedema), with one eye lesion as a secondary effect. The cause of death may have been a direct sequel of the alterations noted in life. Based on these results, the test item is considered to be toxic under the UN GHS Criteria "Category III."

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

99.4 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

From an acute oral toxicity study according to OECD 401, the LD50 for females was determined to be 99.4 mg/kg body weight. Based on this result, classification is warranted for Acute Tox. 3 according to CLP (H301: Toxic if swallowed)