2,6-dimethylcyclohexylamine

Endpoint summary

Description of key information

Based on key study results, the oral LD50 of the test material in rats is >215 and < 261 mg/kg bw(BASF SE 1982), the LC50 (4 h) in male and female rats combined is 3.7 mg/l. No data available for acute dermal toxicity.

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: The study is comparable to OECD Guideline 401 with acceptable restrictions (partly limited documentation, e.g. details on test substance or pH value of tested solution).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Dr. Thomae, Biberach, Germany
Acclimatisation period:1 week
Age: 12 weeks; weight: +-20% of average weight
5 rats per cage
certified food and tap water ad libitum
food withheld 16 h prior to gavage
relative air humidity 30-70%, temperature 20-24°C, dark-light-cycle: 12h/12h

Route of administration:

oral: gavage

Vehicle:

other:

Details on oral exposure:

The test substance was solved in aqeous solution of 0.5% carboxymethyl-cellulose (emulsion)

Doses:

121, 178, 215, 261 mg/kg bw; concentrations: 1.21, 1.78, 2.15, 2.61% (w/v).
Treatment of 5 males and 5 females with a dose of 215 mg/kg bw was performed 3 months later.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Application volume: 10 ml/kg bw
- Duration of observation period following administration: 14 days
- Frequency of observations: serveral times on the day of application, at least once daily thereafter
- Weighing: day 0, 2, 3, 7, 13
- Necropsy of survivors and rats found dead performed: yes
- Other examinations performed: clinical signs

Statistics:

no data

Sex:

male

Dose descriptor:

LD50

Effect level:

> 215 - < 261 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

226 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 215 - < 261 mg/kg bw

Mortality:

Males: all animals in the high dose group died within 24 h, all other rats survived.
Females: 1/5 rats died at 215 mg/kg bw and all rats at the high dose level. Rats died within the 1st 24 h.

Clinical signs:

other: First symptoms occurred 30 minutes after gavage of 261 and 215 mg/kg bw; in survivors the syptoms lasted 4 h; authors described dyspnoea, apathy, staggered gait, atony, side position, twitching and poor general condition. In female rats symptoms (dyspnoea

Gross pathology:

No treatment related effects were detected in survivors and general congestive hyperemia in rats found dead.

Other findings:

no

Comment: alkalinity of test solution not measured; systemic effects not excluded.

Conclusions:

In male and female rats combined the LD50 after gavage was >215 and < 261 mg/kg bw

Executive summary:

The study is comparable to OECD Guideline 401 with acceptable restrictions (partly limited documentation, e.g. details on test substance or pH value of tested solution).

Male and female rats received via gavage the test substance at 4 dose levels (n=5 per dose per sex); the post exposure observation period was 14 days. The test substance resulted in the following clinical signs: dyspnoea, apathy, staggered gait, atony, side position, twitching and poor general condition; survivors appeared normal 4 h after gavage. The LD50 was > 215 and <261 mg/kg bw for both sexes combined.

Conclusion: In male and female rats the oral LD50 was >215 and < 261 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is comparable to OECD Guideline 403

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Dr. Thomae, Biberach, Germany
At initiation the age was 8 weeks and weight of males 263 +- 50 g, and females 178 +- 38 g
5 rats per cage
certified food and tap water ad libitum during post exposure period
relative air humidity 30-70%, temperature 20-24°C, dark-light-cycle: 12h/12h

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

other: air

Details on inhalation exposure:

Vapour-air mixture generated; temperature in exposure chamber 19-24 h; evaporation at 40°C and mixture with air; analytical control every 30 minutes during exposure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC method; calibration; 7-8 samples per concentration

Duration of exposure:

4 h

Concentrations:

analytical means of 7-8 samples: 2.56+-0.9 mg/l, 3.62+-1.8 mg/l, 4.16+-2.16 mg/l

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at least once daily
- weighing: day 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

Probit analysis according to Finney 1971

Sex:

male

Dose descriptor:

LC50

Effect level:

4.1 mg/L air (analytical)

95% CL:

3.7 - 9.5

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 3 mg/L air (analytical)

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

3.7 mg/L air (analytical)

95% CL:

3.5 - 4

Exp. duration:

4 h

Mortality:

In males 5/10, 3/10, and 0/10 at high, mid, and low dose level, respectively.
In females 9/10, 7/10, and 0/10 at high, mid, and low dose level, respectively.
All rats died within 4 h after exposure.

Clinical signs:

other: During exposure: escape behavior, dyspnoea, eye and nose secretion, salivation; pale skin. After exposure: excitation, ruffled coat, bloody nose, staggered gait, tremor. All effects reversible after 2-6 days.

Body weight:

No treatment related effects.

Gross pathology:

Congestion/hyperemia in rats found dead.
No treatment related effects in survivors.

Other findings:

no

LC50 (1 h) in male and female rats combined is 15 mg/l; calculated according to Haber (C x t = k).

Conclusions:

The LC50 (4 h) in male and female rats combined is 3.7 mg/l.

Executive summary:

The study is comparable to OECD Guideline 403.

Ten male and 10 female Wistar rats per dose were exposed to 2.56 +-0.9, 3.62 +-1.8, or 4.16 +-2.16 mg/l for 4 h; the post exposure observation period was 14 days. During exposure escape behavior, dyspnoea, eye and nose secretion, salivation, and pale skin were observed and after exposure excitation, ruffled coat, bloody nose, staggered gait, and tremor. All effects were reversible within 2 -6 days. The LC50 in males was 4.1 mg/l and in females ca. 3 mg/l. No treatment related effects were detected at necropsy.

Conclusion: The LC50 (4 h) in male and female rats combined is 3.7 mg/l.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

3 700 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In a study comparable to OECD Guideline 401 (RL=2)) male and female rats received 121; 178; 215; and 261 mg/kg 2,6-dimethylcyclohexylamine (n=5 per dose per sex) via gavage; the post exposure observation period was 14 days. The test substance resulted in the following clinical signs: dyspnoea, apathy, staggered gait, atony, side position, twitching and poor general condition; survivors appeared normal 4 h after gavage. The LD50 was > 215 and <261 mg/kg bw for both sexes combined.

Acute inhalation toxicity:

Ten Wistar rats per sex and dose were exposed to 2.56, 3.62, or 4.16 mg/l 2,6-dimethylcyclohexylamine (analytical concentration) for 4 h in a study comparable to OECD Guideline 403 (RL=1); the post exposure observation period was 14 days. During exposure escape behavior, dyspnoea, eye and nose secretion, salivation, and pale skin were observed and after exposure excitation, ruffled coat, bloody nose, staggered gait, and tremor. All effects were reversible within 2 -6 days. The combined LC50 3.7 mg/l/4h. No treatment related effects were detected at necropsy.

In another inhalation study (RL = 2) comparable to the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) Wistar rats were exposed to saturated vapour generated at 20°C. The mortality rate was 0/6 males and 0/6 females after 1 h exposure, 2/3 males and 0/3 females after 1.5 h, or 2/3 males and 2/3 females after an exposure duration of 2 h. The symptoms during exposure were closed eyes, dyspnoea, eye and nose secretion, cyanosis, and after exposure breathing sound, crusted nose, unsure gait, apathy, tremor, convulsions, and ruffled coat; in some rats opaque cornea was detected (not reversible in one rat). All effects (except cornea lesion) were reversible after 13 days. No treatment related effects were found at necropsy.

Acute dermal toxicity:

No data available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for acute oral toxicity cat. 3 and acute inhalative toxicity cat. 3 under Regulation (EC) No. 1272/2008.