Trimethyloctadecylammonium chloride

Endpoint summary

Description of key information

Based on the results from the in vivo irritation study, C18 TMAC is considered to be corrosive to skin as well as eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reason / purpose for cross-reference:

data waiving: supporting information

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From January 09, 1996 to February 09, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K. Thomae 88400, Biberach
- Age at study initiation: About 3-5 month
- Weight at study initiation: 2.7-3.8 kg
- Housing: In fully air-conditioned rooms in seperate cages arranged in a battery
- Diet: Ssniff K-H (V2333), ad libitum and hay (approximately 15g daily)
- Water: Automatic water dispensers, ad libitum
- Acclimation period: 1 wk under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3°C
- Humidity: 50 ± 20%
- Photoperiod: 12h light/12h dark

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

0.5g of the test substance pasted with 0.3 mL isotonic saline

Duration of treatment / exposure:

4 hours as well as 3 minutes

Observation period:

Examination of the skin took place after 30-60 minutes as well as 24, 48 and 72 hours after removal of the patches. If the irritation persists 72 hours after removal of the patch (treatment 4h), additional reading were performed after 7, 14 and 22 days.

Number of animals:

1 (treatment 4 hours) and 3 (treatment 3 minutes).

Details on study design:

The substance was applied over the whole surface of a 2.5x2.5 cm cellulose patch on a piece of surgical plaster. The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage. After the exposure, all remnants of the test substance were carefully removed from the skin with warm tap water. Erythema, eschar formation and oedema were evaluated numerically according to the score of DRAIZE. All other changes of the skin were recorded

Irritation parameter:

erythema score

Remarks:

4 h exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

not fully reversible within: 22d

Irritation parameter:

edema score

Remarks:

4 h exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 14d

Irritation parameter:

erythema score

Remarks:

3 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

3 min exposure

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Treatment 4 hours: 30-60 minutes upto 22 days after removal of the plaster the animal showed a very slight to well defined erythema. One day up to 7 days after application a very slight oedema was noted. During the observation period, the treated skin area was sporadically dry, rough, indurated, encrusted, chapped and discoloured large beige. 22 days after application pink coloured new skin and a scar was noted.
Treatment 3 minutes: No sigh of irritation was observed during the whole observation period.

Conclusions:

Under the study conditions, the test substance was found to be corrosive to rabbit skin.

Executive summary:

A study was conducted to determine the skin irritation / corrosion of the test substance, C18 TMAC (79.8% active) according to OECD Guideline 404 and EU Method B.4, in compliance with GLP. A paste containing 0.5 g of the test substance (purity of 79.8%) with 0.3 mL isotonic saline was applied under semi-occlusive patches to the clipped dorsal area of four rabbits. One animal was exposed for 4 h and three animals were exposed for 3 min. The test sites were examined for evidence of primary irritation and scored according to Draize method. No signs of irritation were observed during the whole observation period after exposure to 3 min. However, a 4 h exposure resulted in slight to well defined erythema and a slight oedema, visible 30-60 min up to 22 days after removal of the plaster. Between one and seven days after application, slight oedema was noted. During the observation period, the treated skin area was sporadically dry, rough, indurated, encrusted, chapped and discoloured. Twenty-two days after application, pink coloured new skin and a scar was noted. Under the study conditions, the test substance was found to be corrosive to rabbit skin (Kreiling, 1996).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

A study was conducted to determine the skin irritation / corrosion of the test substance, C18 TMAC (79.8% active) according to OECD Guideline 404 and EU Method B.4, in compliance with GLP. A paste containing 0.5 g of the test substance (purity of 79.8%) with 0.3 mL isotonic saline was applied under semi-occlusive patches to the clipped dorsal area of four rabbits. One animal was exposed for 4 h and three animals were exposed for 3 min. The test sites were examined for evidence of primary irritation and scored according to Draize method. No signs of irritation were observed during the whole observation period after exposure to 3 min. However, a 4 h exposure resulted in slight to well defined erythema and a slight oedema, visible 30-60 min up to 22 days after removal of the plaster. Between one and seven days after application, slight oedema was noted. During the observation period, the treated skin area was sporadically dry, rough, indurated, encrusted, chapped and discoloured. Twenty-two days after application, pink coloured new skin and a scar was noted. Under the study conditions, the test substance was found to be corrosive to rabbit skin (Kreiling, 1996).

Eye

In accordance with Annex VII, Section 8.2, Column 2, eye irritation studydoes not need to be conducted because the substance is classified as corrosive to the skin.

Justification for classification or non-classification

Based on the results of thein vivoskin irritation study, the test substance warrants a corrosive, ‘Skin Corr. 1C; H314: Causes severe skin burns and eye damage’ as well as serious eye damage, ‘Eye dam. 1; H31: Causes serious eye damage’ classification according to the EU CLP criteria (Regulation EC 1272/2008). Labelling for this endpoint is covered by the above classifications for skin effects. 

With regard to respiratory tract irritation, although C18 TMAC is a very corrosive substance, its low vapour pressure prohibits the occurrence of respiratory irritation by vapour. Further, the classification of corrosive is already considered to implicitly cover the potential of RTI; therefore, an additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5).