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Description of key information

The studies available for the related substances of reaction mass of isomers of: C7 -C9 -alkyl 3 -(3,5 -di-tert-butyl-4hydroxyphenyl) propionate indicate slight irritation potential of the test material. In the skin irritation studies conducted in rabbits, a 4 -hour semi-occluded application of test material to the skin of animals produced very slight to well-defined erythema and very slight oedema. All skin reactions were fully reversible within 7 days. According to the Draize classification scheme, the tested substances were classified as mild irritants to rabbit's skin. Slight skin irritation potential of target chemical, predicted by the OECD QSAR Toolbox, confirms these results (calculated Primary Irritation Index of 1.63). 
In the eye irritation studies, instillation of 0.1 mL of undiluted test material to the non-irrigated eye of rabbits produced minimal or moderate conjunctival irritation which was fully reversible within 24 - or 72 hours of observation. No corneal reactions were noted in treated animals during the studies. According to the modified Kay and Calandra classification system, the substances were classified as mild irritant (CAS No. 144429 -84 -5) and minimal irritant (CAS No. 524439 -44 -2) to the rabbit eye. According to the modelling results by the OECD QSAR Toolbox, MMAS of 8.00 was predicted for the target chemical, what indicates slightly irritation potential. No structural alerts were identified responsible for irritation properties by the Toxtree modelling tool.
According to the CLP criteria (CLP Regulation (EC) No. 1272/2008) the test substance has no skin and eye irritant properties in laboratory animals.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

To assess irritation potential of reaction mass of isomers of: C7 -C9 -alkyl 3 -(3,5 -di-tert-butyl-4hydroxyphenyl) propionate the following irritation studies on the related substances were used:

Acute Dermal Irritation Study in the Rabbit conducted with Butyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate (CAS No. 52449 -44 -2)

A GLP study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit (Driscoll, 2000; Report No. 525/204). The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. A mean score of 0.7 for erythema/eschar formation was recorded in each, the first and the second animal. In the third animal, the mean score was 1.7. The mean scores for oedema formation were 0.0, 0.0 and 0.7 for animal 1, 2 and 3, respectively. Loss of skin elasticity was noted at two treated skin sites. All treated skin sites appeared normal at the end of the 7-day observation. The test material produced a primary irritation index of 1.0 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations (EU Directive 67/548/EEC). No symbol and risk phrase were required.

Acute Dermal Irritation in the Rabbit conducted with (Benzenepropanoic acid, 3,5 -bis(1,1 -dimethylethyl)-4 -hydroxy-,2 -ethylhexylester (CAS No. 144429 -84 -5)

A GLP study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit (Sanders, 2007; Report No. 0525/0754). The method was designed to meet the requirements of the OECD guideline 404 and EU method B.4. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. One treated skin site appeared normal at the 72-hour observation and the remaining two treated skin sites appeared normal at the end of the 7-day observation. The test material produced a primary irritation index of 1.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 2001/59/EC.

Acute Eye Irritation Test in the Rabbit conducted with Butyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate (CAS No. 52449 -44 -2)

A GLP study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit (Driscoll, 2000; Report No. 525/205). The method used followed that described in the OECD guideline 405 and in the EU Method B.5. A single instillation of 0.1 mL of undiluted test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal at the end of the 24-hour observation. No control animals were used. One eye of each animal remained untreated and was used for control purposes. The test material produced a maximum group mean score of 5.3 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as irritant according to EU labelling regulations (Directive 67/548/EEC). No symbol and risk phrase were required.

Acute Eye Irritation in the Rabbit conducted with (Benzenepropanoic acid, 3,5 -bis(1,1 -dimethylethyl)-4 -hydroxy-,2 -ethylhexylester (CAS No. 144429 -84 -5)

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit (Sanders, 2007; Report No. 0525/0755). The method was designed to meet the requirements of the OECD Guideline 405 and EU Method B.5. A single application of 0.1 mL of undiluted test material to the non-irrigated eye of three rabbits produced iridial inflammation and moderate conjunctival irritation. One treated eye appeared normal at the end of the 48 -hour observation and the remaining two treated eyes appeared normal at the end of the 72 -hour observation. The test material produced maximum group mean score of 10.7 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC.

Prediction of skin and eye irritation potential by the TOXTREE modelling tool (v2.1.0)

The chemical structure of the C9 -representative of the reaction mass of isomers (nonyl-3(3,5 -ditert-butyl-4 -hydroxyphenyl)propanoate)

was assessed by Toxtree (v.2.1.0) modelling tool for its skin and eye irritation potential. The test chemical is estimated to be not corrosive and not irritating to skin and eyes. For the estimations the melting point of 186°C and water solubility of 0.0003 mg/L, both calculated by EPIWIN modelling tool for the target chemical, were put into the Toxtree modelling tool.

Prediction of skin and eye irritation potential by the OECD QSAR Toolbox

Skin irritation potential

The chemical benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, C7-9-branched alkyl esters (CAS 125643-61-0) was evaluated by the QSAR OECD Toolbox software for its skin irritation potential. The prediction was based on the measured values of chemicals assigned into the category. The experimental data for the related chemicalsbutyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate (CAS 52449 -44 -2) and benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-,2-ethylhexylester (CAS 144429 -84 -5) were added in the software manually and together with data of other structurally similar analogues were used for the read-across.

The target chemical was classified as "Phenols, Esters" by the profiling method "Aquatic toxicity classification by ECOSAR ". Therefore, at first the chemicals with the same classification were searched. 122 chemicals (inclusive manually added data of two chemicals) were assigned into the category. There were several chemicals in the category for which data are available for the investigated endpoint. These chemicals were scanned for their differences to the target and thereafter the category was refined eradicating chemicals with different characteristics relevant for skin irritation. In this manner, the chemicals were eliminated which possess different organic functional groups (performed by the "Organic functional groups (US EPA)"). The selected 4 neighbour chemicals which were used for read-across represent the same class of chemicals and exhibit the same irritation potential. Primary irritation index (PII) of 1.63 was predicted for the target chemical. According to the PII grading system 1.63 indicates slightly irritating potential. However, individual scores and grouping scores in treated animals (as indicate data of two nearest analogues CAS 52449 -44 -2 and CAS 144429 -84 -5) do not meet criteria for classification and labelling as irritant or corrosive to skin according to the CLP Regulation (EC) No. 1272/2008. The other two chemicals in the category (CAS 6386 -38 -5 and CAS 2082 -79 -3) are also not irritating or corrosive to skin.

Eye irritation potential

The chemical benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, C7-9-branched alkyl esters (CAS 125643-61-0) was evaluated by the QSAR OECD Toolbox software for its eye irritation potential. The prediction was based on the measured values of chemicals assigned into the category. The experimental data for the related chemicals butyl 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoate (CAS 52449 -44 -2) and benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-,2-ethylhexylester (CAS 144429 -84 -5) were added in the software manually and together with data of other structurally similar analogues were used for the read-across.

The target chemical was classified as "Phenols, Esters" by the profiling method "Aquatic toxicity classification by ECOSAR ". Therefore, at first the chemicals with the same classification were searched. 122 chemicals (inclusive manually added data of two chemicals) were assigned into the category. Except data of manually included chemicals there were no other chemicals in the category for which data were available for the investigated endpoint. Modified maximum average score of 8.00 was predicted for the target chemical. According to the modified Kay and Calandra classification system 8.00 indicates minimal irritating potential to the rabbit eye. However, individual scores and grouping scores in animals treated with either nearest analogue CAS 52449 -44 -2 or CAS 144429 -84 -5 do not meet criteria for classification and labelling as irritant or corrosive to eyes according to the CLP Regulation (EC) No. 1272/2008.

 


Justification for selection of skin irritation / corrosion endpoint:
The most recent study available.

Justification for selection of eye irritation endpoint:
The most recent study available.

Justification for classification or non-classification

Skin Irritation/corrosion

The overall weight of evidence signify that experimentally obtained values for two structural analogues allow to draw a conclusion about skin irritation properties of reaction mass of isomers of: C7 -C9 -alkyl 3 -(3,5 -di-tert-butyl-4 -hydroxyphenyl)propionate. The nearest analogues were classified as mild irritants to the rabbit skin according to Draize. However, individual daily and mean scores for dermal irritation do not meet criteria for classification and labelling according to the CLP Regulation (EC) No. 1272/2008.

Eye Irritation/corrosion

Due to the fact that conjunctivae score of 1.0 was recorded for only one animal (Sanders, 2007), reaction mass of isomers of: C7 -C9 -alkyl 3 -(3,5 -di-tert-butyl-4 -hydroxyphenyl)propionate does not meet the criteria for classification and labelling as irritant or corrosive to eyes according to the CLP Regulation (EC) No. 1272/2008.

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