Reaction mass of dodecyl methacrylate and tridecyl methacrylate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL (reproduction/development) = 1000 mg/kg bw/d (no adverse effects on fertility and development) (OECD TG 422, rat, oral gavage, RL1, GLP); read-across from Dodecyl methacrylate

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physicochemical, ecotoxicological and toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: methacrylate esters
• the metabolism pathway leads to comparable products (methacrylic acid and medium chain alcohol).

Therefore, read-across from the existing physicochemical, ecotoxicity and toxicity studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed up to limit dose

Critical effects observed:

no

Remarks on result:

not measured/tested

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

CLINICAL SIGNS (OFFSPRING)
Coldness to the touch was noted in seven pups (one litter) in the control group and four pups (three litters) at 1000 mg/kg/day. This sign was
considered not to be related to treatment since it was observed at a greater incidence in the control group.
The other clinical signs (anouria in one pup from the control group, necrosed forelimb in one pup from the 300 mg/kg/day group) were considered not to be treatment-related as they were isolated findings.

BODY WEIGHT (OFFSPRING)
There was no effect of treatment on mean pup body weight or body weight gain for males or females.

SEX RATIO (OFFSPRING)
The sex ratios on days 1 and 5 post-partum were similar in the control and test item-treated groups, and close to a theoretical value of 50%.
GROSS PATHOLOGY (OFFSPRING)
No relevant findings were observed in the pups sacrificed on day 6 post-partum or in the pups found dead.

Dose descriptor:

NOEL

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed up to limit dose

Remarks on result:

not measured/tested

Reproductive effects observed:

no

Conclusions:

On the basis of the results the NOEL(reproduction/developmental) was considered to be >= 1000 mg/kg bw/day in males and females.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No experimental data on Reaction mass of dodecyl methacrylate and tridecyl methacrylate are available for the assessment of toxicity to reproduction. However, studies are available for the source substance Dodecyl methacrylate. A detailed justification for read-across is attached to IUCLID section 13.

 

Summary

Dodecyl methacrylate did not elicit any signs of toxicity when administered to Sprague-Dawley rats at 100, 300 or 1000 mg/kg/day in a combined repeated dose toxicity study with the reproduction / developmental toxicity screening test. Based on the experimental conditions of this study, the No Observed Adverse Effect Level (NOAEL) for parental toxicity was considered to be 1000 mg/kg/day and the No Observed Effect Level (NOEL) for toxic effect on reproductive performance and on developmental toxicity was greater than or equal to 1000 mg/kg/day.

 

Hypothesis for the analogue approach

The read-across hypothesis relies on the close structural similarity between the source substance Dodecyl methacrylate and the target substance Reaction mass of dodecyl methacrylate and tridecyl methacrylate. This read-across hypothesis corresponds to scenario 2 - different compounds have qualitatively similar properties - of the read-across assessment framework i.e. properties of the target substance are predicted to be quantitatively equal to those of the source substance. Namely, the structurally similar source substance Dodecyl methacrylate predicts the toxicological properties of the target substance Reaction mass of dodecyl methacrylate and tridecyl methacrylate.

 

Based on the available data, including physicochemical data (water solubility and log Kow) and acute oral toxicity, the read-across strategy is supported by close structural analogy and similar toxicological profile of the substances.

 

Toxicological data are summarised in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.

 

Therefore, read-across from the existing toxicity studies conducted with the source substance is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A detailed justification for the proposed read-across approach is attached to Iuclid section 13.

 

1. Identity and characterisation of the source substance

There is close structural similarity between the source and the target substances and the identity and characterisation of these substances is unambiguous thereby giving a high level of confidence in the validity of the read across.

The target and source substances are manufactured from similar compounds by esterification of methacrylic acid with the corresponding fatty alcohol. Typical trace impurities are water and the corresponding alcohols as well as < 1 % methacrylic acid, which are not of toxicological concern.

The carbon chain length distribution of the resulting mix of long-chain aliphatic methacrylate esters mirrors the chain length distribution of the alcohol(s) used.

 

2. Link of structural similarities and differences with the proposed prediction

Structural similarities:

The target substance Reaction mass of dodecyl methacrylate and tridecyl methacrylate is an ester of Methacrylic acid and mainly linear C12 / C13 alcohols. The source substance Dodecyl methacrylate is comparable to the target substance with respect to chain length and contains only linear C-chains.

 

Structural differences:

The difference alkyl chain length between the target and the source substance is negligible.

The physicochemical properties (both substances have a log Kow > 6.5 and a water solubility < 1 µg/L) are very similar. Thus, no large differences in bioavailability are expected.

The target substance contains small amounts of branched alkyl chains, which is not considered toxicologically relevant.

The presence of branches in close proximity to the ester function is likely to have a negative influence on hydrolysis rates due to steric hindrance. Branching in more remote positions did not have a pronounced effect on hydrolysis rates (Jones, 2002). Therefore, is can be concluded, that the presence of branched alkyl chains in the target substance is not likely to influence ester cleavage.

In general, branched fatty alcohols are not expected to exhibit higher toxicity than linear fatty alcohols, as branched fatty alcohols are abundant in the diet and are metabolised via the fatty acid α-oxidation and β-oxidation pathways.

 

Consistency of properties in the data matrix

The results of the acute oral toxicity studies demonstrate a low acute toxicity for the target and the source substances.

 

Reliability and adequacy of the source data

All available studies have been conducted according to OECD guidelines and have been assigned a reliability of 1 or 2 as documented in the data matrix (see detailed justification for read-across attached to Iuclid section 13).

 

Overall, the study design of the respective source studies is adequate and reliable for the purpose of this read-across. The results of the selected key studies are adequate for classification and labelling and for risk assessment purposes.

 

Data availability

In an OECD Guideline 422 study Lauryl Methacrylate (Lauryl MA; CAS RN 142-90-5), was administered to male and female Sprague-Dawley rats by the oral route (gavage) at the dose-levels of 100, 300 or 1000 mg/kg/day. At 1000 mg/kg/day, hypersalivation was recorded in males and females, lower body weight gain was recorded in females during the GD 0-7 interval and increased plasma glucose concentrations were recorded in males. At 300 mg/kg/day, a few animals had hypersalivation. At 100 mg/kg/day, no treatment-related effects were detected. Hypersalivation was not considered to be a sign of toxicity to Lauryl MA. There were no substance-induced effects on the male and female reproductive performance, nor on the progeny of the parental rats at any dose-level. There were no treatment-related findings at histopathological examination. Based on the experimental conditions of this study, the No Observed Adverse Effect Level (NOAEL) for parental toxicity was considered to be 1000 mg/kg/day and the No Observed Effect Level (NOEL) for toxic effect on reproductive performance and on developmental toxicity was greater than or equal to 1000 mg/kg/day.

 

 

There are no data gaps for the endpoint toxicity to reproduction. There is no reason to believe that the results would not be relevant to humans. 

 

Justification for classification or non-classification

Based on the available data, Reaction mass of dodecyl methacrylate and tridecyl methacrylate does not need to be classified for toxicity to reproduction according to the criteria given in regulation (EC) 1272/2008. Thus, no labelling is required.