Butyl nitrite

Endpoint summary

Description of key information

Acute oral toxicity: Key study. Test method similar to OECD 401. The LD50 of the test item is 83 mg/kg body weight by oral route in the rat.

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:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(no data on source of animals and environmental conditions; no data on observation period)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: COBS: CD, Charles River

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: average weight of 229.9 g (SD. 10.97; range 208-254)
- Fasting period before study: from afternoon preceding the day of dosing
- Housing: individually in suspended cages at 71ºF for several days.
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 71ºF
- Photoperiod (hrs dark / hrs light): 12h day-night cycle.

Route of administration:

oral: gavage

Vehicle:

ethanol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 1 ml/kg bw
- Justification for choice of vehicle: Commercial products containing butyl nitrite may contain amounts of the aliphatic alcohols (e.g. butyl alcohol) from which they are synthesized and to which they degrade on standing. Butyl alcohol itself has an oral LD50 for the rat of 790 mg/kg, thus it is 17.2 times more toxic than ethanol (LDS0: 13.6 g/kg). Therefore, ethanol was used as a vehicle in order to determine the LD50 of butyl nitrite in the absence of significant vehicle effects.
- Purity: 95%

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A preliminary estimate of the LD50 was obtained by the Robbins-Monro procedure. An initial dose is given to 2 rats. If one of the two died, the dose was repeated. If both survived, the dose was increased; if both died, the dose was decreased. Eight pairs of animals were dosed in this manner, the next dose in the sequence being taken as the best estimate of the LD50. This dose was used to select three additional doses that were administered to an additional 28 rats (main study). These doses were selected to bracket the LD50, so that estimates of the slope of the function could be generated.

Doses:

Preliminary study: initial dose of 100 mg/kg bw
Main study: 78, 88 and 100 mg/kg bw

No. of animals per sex per dose:

Preliminary study: 2 males per dose (16 males in total)
Main study: 10, 9 and 9 males for doses of 78, 88 and 100 mg/kg bw respectively

Control animals:

no

Details on study design:

- Duration of observation period following administration: not specified
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: not specified
- Other examinations performed: clinical signs

Statistics:

Logit analysis

Preliminary study:

The Robbins-Monro procedure indicated the LD50 to be 80.75 mg/kg bw.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

82.99 mg/kg bw

Based on:

test mat.

95% CL:

>= 79.49 - <= 86.49

Key result

Sex:

male

Dose descriptor:

LD0

Effect level:

76.44 mg/kg bw

Based on:

test mat.

Mortality:

the observed deaths were 1/10, 8/9 and 9/9 for de dosing levels of 78, 88 and 100 mg/kg bw respectively.

Clinical signs:

Death produced by butyl nitrite was preceded by a grey pallor of the extremities, labored breathing, ataxia, extensor rigidity and fasciculations. At higher doses, death occurred within 40 min; at doses very close to the LD50, death was delayed, in a few instances, to approximately three hours. If the animal recovered from this ataxic phase, survival was assured for two weeks.

Body weight:

changes in body weights not recorded.

Gross pathology:

not specified

Interpretation of results:

other: classified as acute toxicity cat. 3 (CLP Regulation EC no. 1272/2008)

Conclusions:

The LD50 of the test item is 83 mg/kg body weight by oral route in the rat.

Executive summary:

The acute oral toxicity of the test item was performed similarly to OECD Test Guideline 401. Male white rats (COBS : CD, Charles River) were used for this study. A preliminary estimate of LD50 was obtained by the Robbins-Monro procedure using 16 animals. Based on this result, the doses chosen for the main experiment were 78, 88 and 100 mg/kg bw administered by gavage on 10, 9 and 9 rats, respectively. The test item was dissolved in 95% ethanol which was used as vehicle due to its low toxicity. The proportions of deaths found in the main assay were 1/10, 8/9 and 9/9 for the doses of 78, 88 and 100 mg/kg bw, respectively. Deaths were preceded by a grey pallor of the extremities, labored breathing, ataxia, extensor rigidity and fasciculations. At doses of 76.44 mg kg bw and below, no fatalities were observed. The LD50 calculated by logit analyis was estimated to be 82.99 mg/kg bw (95% CL: 79.49-86.49).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

83 mg/kg bw

Quality of whole database:

Key study with Klimisch score = 2

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity: Key study: The acute oral toxicity of the test item was performed similarly to OECD Test Guideline 401. Male white rats (COBS : CD, Charles River) were used for this study. A preliminary estimate of LD50 was obtained by the Robbins-Monro procedure using 16 animals. Based on this result, the doses chosen for the main experiment were 78, 88 and 100 mg/kg bw administered by gavage on 10, 9 and 9 rats, respectively. The test item was dissolved in 95% ethanol which was used as vehicle due to its low toxicity. The proportions of deaths found in the main assay were 1/10, 8/9 and 9/9 for the doses of 78, 88 and 100 mg/kg bw, respectively. Deaths were preceded by a grey pallor of the extremities, labored breathing, ataxia, extensor rigidity and fasciculations. At doses of 76.44 mg kg bw and below, no fatalities were observed. The LD50 calculated by logit analyis was estimated to be 82.99 mg/kg bw (95% CL: 79.49-86.49).

Justification for classification or non-classification

Based on the available data, the substance is classified for acute toxicity cat. 3 according to CLP Regulation (EC) no. 1272/2008.