2-amino-2-methylpropanol

Endpoint summary

Description of key information

Skin:

Phys-chem information: The test item's pH and pKa suggest a skin irritant potential (see correspodning data, weak alkaline material).

Animal data: 5 rabbit studies are available, all non-guideline, pre-GLP and with significant deviations. However, weight-of-evidence conclusion is possible:

1. 1940 5-day study on neutralized AMP dilutions (10%, 25%): disregarded due to pH neutralisation before application - hence, the absence of any skin irritation does not allow to draw any conclusion


2. 1940 5-day study on neat AMP: suboptimal exposure pattern, notably no occlusion - hence, the absence of "significant skin irritation" only allows to exclude skin corrosion


3. 1975 studies on skin corrosion (US DOT method), reported in 1976+2001, on AMP-Regular and AMP-95: slightly excessive exposure (4 hour) targetting skin corrosion endpoint only - hence, the only conclusion drawn is "non corrosive"


4. 1976 secondary citation: "Undiluted P-1826 is considered a severe skin irritant having an irritation index of 6.1 (six rabbits).", no further details avaialble, Klismisch 4 - hence, this only allows to exclude "non classified"


5. 1980 acute dermal toxicity study on neat AMP: very excessive exposure (24h exposure vs. minutes or hours required) - hence, the observed irreversible skin damage only allows to exclude "non classified"

Based on 2 studies excluding skin corrosion cat 1 (1940, 1975) and 2 studies excluding "not classified" (1976, 1980), WOE allows to conclude on classification as "Skin irritant cat 2".

Human data (section 7.10.4): Cipolla et al (1997) reported two cases of airborne skin dermatitis in a cosmetic factory using AMP-100. Patch testing in exposed workers and control workers evidenced that these skin reactions were skin irritation and not skin sensitisation, because they only occured at high test concentrations (>=10% AMP in water or ethanol) and because pre-exsisting exposure to AMP did not lead to significantly worse skin reactions. The dose-response proves that AMP is not a corrosive substance and should be labelled as Skin irritant cat 2.

Eyes:

In a study designed to assess the irritancy to eyes, AMP was applied to the eyes of 12 rabbits undiluted. In six of the rabbits, the AMP was washed out 15-30 seconds after dosing. In this study AMP caused serious damage to the eyes and ultimately destroyed the vision (Power, 1975b). The damage was not mitigated even with an immediate flushing of the eyes. The serious occular damage is likely the result of the high pH of the compound instead of any inherent toxicity based on the chemical structure.

A set of empirical rules were concluded based on weight-of-evidence assessment of structure, pH, pKa and skin/eye irritation information for a category of 16 aminoalcohols. Application of 4 of these rules to predict eye/skin effects of AMP and its secondary amine impurity MMAMP:

1. Skin to Eye: AMP and MMAMP are both skin irritants cat 2, so they are at least eye irritants cat 2, and Eye damage 1 cannot be ruled out


2. pKa: AMP pKa 9.8 leads to predicting it as Eye damage 1


3. pH: AMP pH 12.2 and MMAMP pH 12.5 leads to predicting both as Eye damage 1


4. Structure: AMP and MMAMP are C4/C5 aminomonoalcohols, leading to predicting both as Eye damage 1

Final prediction is, both AMP and MMAMP are Eye damage 1.

Overall this confirms and that the CLP harmonized classification as Eye Irritant 2 is incorrect. ECHA has been informed on 24^th October 2022 via a CLH intention notification, it is now up to Member States to act by submitting a CLH dossier.

Respiratory Tract:

Studies of the potential irritant characteristics of inhaled AMP have been undertaken using the ATSM E981 sensory irritation methodology. Restrained mice were head-only exposed up to 1160 mg/m3 aerosolized AMP for 3 hours followed by a 20 minute recovery period (Detwiler-Okabayashi and Shaper, 1996). No deaths were recorded but sensory and pulmonary irritation of mice was noted. However, the study is not relevant for classification because AMP has low vapour pressure so such an extreme exposure can only be achieved with aerosols.

Effects on skin irritation/corrosion: skin irritant cat 2

Effects on eye irritation: eye damage 1

Effects on respiratory irritation: no relevant data (but unlikely based on vapour pressure)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the above data and in accordance with CLP criteria, AMP is self-classified as:

- Skin Irritation 2.

- Eye Damage 1. The CLP harmonized classification as Eye Irritant 2 is incorrect. ECHA has been informed on 24^th October 2022 via a CLH intention notification, it is now up to Member States to act by submitting a CLH dossier.