1,3,3-trimethyl-N-(2-methylpropylidene)-5-[(2-methylpropylidene)amino]cyclohexanemethylamine

Endpoint summary

Description of key information

1,3,3 -Trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene) amino]cyclohexane-methylamine is of oral and dermal acute toxicity with an oral LD50 (rat) of 4150 mg/kg bw (Hüls AG, 1985) and a dermal LD50 > 5000 mg/kg bw (Hüls AG, 1985).

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:

1985-06-12 to 1985-07-02

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:

(1981)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

3160; 3980; 5010; 6310 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 150 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 517 - <= 4 897

Mortality:

- Number of deaths at each dose:
  3160 mg/kg bw: 0 males, 2 females dead within 26 hours
  3980 mg/kg bw: 1 male, 4 females dead within 24 hours
  5010 mg/kg bw: 2 males, 3 females dead within 48 hours
  6310 mg/kg bw: 5 males, 4 females dead within 30 hours

Clinical signs:

other: - 30 minutes after application: Ruffled fur - later: Crouched posture, some cases of slight sedation and ataxia,  staggering gait, prone position, cyanosis of the extremities,  hypothermia, and narrowed or closed palpebral fissures - at 24 hours (additi

Gross pathology:

- animals that died during the study: Swelling of the gastric mucosa,  hyperemia of the gastric and intestinal mucosa, the peritoneum and the  diaphragm, and of the pancreas; formation of flecks on liver and kidneys
- terminal necropsy: Areas of whitish fur on the cardial mucosa,  discoloration of the liver, conglutination and fusion of the abdominal  organs with one another and with the diaphragm

Conclusions:

The LD50 value (oral) of 1,3,3 -Trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene)amino]cyclohexanemethylamine in female and male rats was estimated to be 4150 mg/kg bw. Therefore, under the conditions employed in this study, the acute toxicity after oral exposure in rats is low.

Executive summary:

1,3,3 -Trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene)amino]cyclohexanemethylamine is of low oral acute toxicity with an oral LD₅₀(rat) of 4150 mg/kg bw (OECD 401, Hüls AG, 1985). Mortalities were observed in the oral acute toxicity study at doses > 3160 mg/kg bw. Clinical signs after oral administration like ruffled fur 30 min after application, later: crouched posture, some cases of slight sedation and ataxia, staggering gait, prone position, cyanosis of the extremities, hypothermia, and narrowed or closed palpebral fissures. At 24 h additional observations, like diarrhea and increased diuresis were made. In the two highest dose groups (i.e. 5010 and 6310 mg/kg bw respectively), difficulties with breathing, uttering sounds when touched and towards the end of the study ruffled fur in 2 animals from the high dose group were observed. Other signs disappeared approximately by day 10.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 150 mg/kg bw

Quality of whole database:

The study is reliable without restriction (Klimisch score 1)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

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:

1985-06-11 to 1985-06-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Strain: Bor: WISW (SPF TNO)
- Source: F. Winkelmann, Borchen (Germany)
- Weight at study initiation: 5 males mean 229 g, 5 females mean 213 g

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

- Area covered: dorsal skin (shaved 24 hours in advance)
- Occlusion: mull patch, elastic dressing (for 24 hours)

Duration of exposure:

- Removal of test substance: after patch removal (at 24 hours), thorough washing with  warm water and swabbing with cellulose
- Post dose observation period: total duration 14 days

Doses:

5000 mg/kg bw (selection based on pre-test performed from 1985-05-21 to 1985-06-12)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

EXAMINATIONS: 
- Body weights: before, and 1, 7, 14 days post dosing
- Clinical signs and mortality: within 6 hours after dosing, thereafter  daily
- Necropsy: all animals (macroscopic)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No deaths

Clinical signs:

other: - immediately after treatment: Vehement defense reactions, uttering  sounds, both attributed to fixation of patch - at 1 hour: Ruffled fur, stretched posture, temporary uttering sounds,  Straub reaction, reddish brown color of application area - after p

Gross pathology:

Hyperemia of the small intestinal mucosa and in one  animal formation of flecks on the kidneys

Conclusions:

The LD50 value (dermal) of 1,3,3 -Trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene)amino]cyclohexanemethylamine in female and male rats was estimated to be > 5000 mg/kg bw. No mortalities were observed. Therefore, under the conditions employed in this study the substance is of low dermal acute toxicity.

Executive summary:

1,3,3 -Trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene)amino]cyclohexanemethylamine is of low dermal acute toxicity with a dermal LD₅₀of > 5000 mg/kg bw (OECD 402, Hüls AG, 1985).

For the dermal acute toxicity study no mortalities up to a dose of 5000 mg/kg bw were observed. Clinical signs immediately after treatment were vehement defense reactions, uttering sounds, both attributed to fixation of the patch. At 1 hour the following observations were made: ruffled fur, streched posture, temporary prone position or retarded motion, staggering gait, hypothermia and slight sedation. In the application area necrosis, incrustation of application area, wounds partly with discharge, and formation of scars were observed.

Necropsy findings were Hyperemia of the small intestinal mucosa and in one animal formation of flecks on the kidneys. The body weight was transiently inhibited.

Dermal exposure has to be avoided because of sensitizing properties.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The study is reliable without restriction (Klimisch score 1)

Additional information

1,3,3 -Trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene)amino]cyclohexanemethylamine is of low oral and dermal acute toxicity with an oral LD₅₀(rat) of 4150 mg/kg bw (OECD 401, Hüls AG, 1985) and a dermal LD₅₀ of > 5000 mg/kg bw (OECD 402, Hüls AG, 1985) . Mortalities were observed in the oral acute toxicity study at doses > 3160 mg/kg bw. Clinical signs after oral administration like ruffled fur 30 min after application, later: crouched posture, some cases of slight sedation and ataxia, staggering gait, prone position, cyanosis of the extremities, hypothermia, and narrowed or closed palpebral fissures. At 24 h additional observations, like Diarrhea and increased diuresis were made. In the two highest dose groups (i.e. 5010 and 6310 mg/kg bw respectively), difficulties with breathing, uttering sounds when touched and towards the end of the study ruffled fur in 2 animals from the high dose group were observed. Other signs disappeared approximately by day 10.

For the dermal acute toxicity study no mortalities up to a dose of 5000 mg/kg bw were observed. Clinical signs immediately after treatment were vehement defense reactions, uttering sounds, both attributed to fixation of the patch. At 1 hour the following observations were made: ruffled fur, streched posture, temporary prone position or retarded motion, staggering gait, hypothermia and slight sedation. In the application area necrosis, incrustation of application area, wounds partly with discharge, and formation of scars were observed.

Necropsy findings were Hyperemia of the smal intestinal mucosa and in one animal formation of flecks on the kidneys. The body weight was transiently inhibited.

Dermal exposure has to be avoided because of sensitizing properties.

Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
According to REACH Annex VIII , Column 1, Chapter 8.5, the substance was tested via the oral and dermal route of exposure. Therefore a testing via the inhalative route of exposure is not necessary.

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Based on the results of the acute oral and dermal studies and according to the criteria of EC Directive 67/548/EEC and EC Regulation 1272/2008 1,3,3 -trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene)amino]cyclohexanemethylamine has only low acute toxicity if swallowed or dermally applied. Therefore, the test substance must not be classified.