Registration Dossier

Administrative data

Description of key information

Acute oral toxicity, LD50 (oral) of Modified Small Vinyl Ester was determined experimentally to larger than 5000 mg/kg bw (criteria in OECD 423). The relative dermal absorption rate is less than 0.00014%. The acute dermal study is waived on the basis that this low dermal absorption rate will result in acute dermal toxicity, LD50 much larger than 2000 mg/kg bw. The vapour pressure of Modified Small Vinyl Ester is extremely low and inhalation will result in insignificant internal dose levels, i.e. systemic bioavailability is negligible by inhalation.

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:
8 February 2010 to 22 March 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with a minor protocol deviation and compliant with GLP. The study integrity was not affected by the deviations.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
deviations from the minimum level of relative humidity occurred
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
deviations from the minimum level of relative humidity occurred
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
deviations from the minimum level of relative humidity occurred
Qualifier:
according to
Guideline:
other: JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions
Deviations:
yes
Remarks:
deviations from the minimum level of relative humidity occurred
GLP compliance:
yes
Test type:
acute toxic class method
Species:
rat
Strain:
Wistar
Sex:
female
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 animals per dose group
Control animals:
no
Details on study design:
single dosage on Day 1.Observations until day 15.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: According the OECD guideline 423 the LD50 cut-off value is considered to larger than 5000 mg/kg bw
Mortality:
no mortality occurred
Clinical signs:
piloerection was noted in three animals on Day 1. In addition one animal showed hunched posture on Day 1 and 2.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The oral LD50 value of Modified Small Vinyl Ester in Wistar rats was established to exceed 2000 mg/kg bw.According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg bw.
Executive summary:

Modified Small Vinyl Ester was tested for acute oral toxicity using the acute toxic class method (OECD guideline 423) with a minor protocol deviation and compliant with GLP. The study integrity was not affected by the deviations.

The oral LD50 value of Modified Small Vinyl Ester in Wistar rats was established to exceed 2000 mg/kg bw.

According to the OECD test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Sufficient to meet requirements

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Acute inhalation testing is waived on the basis that the substance has a very low vapour pressure as estimated by QSAR (US-EPA EPIsuite v4.0, cf. IUCLID section 13, assessment reports.001). Various constituents all have vapour pressures below 2E-10 Pa. The residual monomer methacrylic acid (<0.5 % of Modified Small Vinyl Ester) has a vapour pressure of 132 Pa. Thus, it is evaluated that inhalation of vapours in significant amounts is unlikely.Furthermore, Modified Small Vinyl Ester is placed on the market as an approximately 50% solution in a reactive diluent, e.g. styrene, for industrial and professional use only. Spray application of the marketed Modified Small Vinyl Ester will release aerosols. Measurements of the aerosol particle sizes showed that the particles are too large to be inhaled, even after the reactive diluent (e.g. styrene) has evaporated, cf. the attached document. Application of the marketed product requires use of personal protection equipment due to the content of reactive diluent. Furthermore, respirators are prescribed for work processes that generate aerosols.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
This study is waived on the basis that the overall relative dermal penetration was calculated to less than 0.00014%, cf. IUCLID section 7.1.2. Taken together with the very low toxicity seen in the acute oral study, it is foreseeable that the result of acute dermal toxicity testing will be that the LD50 is much larger than 2,000 mg/kg bw.

Additional information

Modified Small Vinyl Ester was tested for acute oral toxicity using the acute toxic class method (OECD guideline 423) with a minor protocol deviation and compliant with GLP. The study integrity was not affected by the deviations. The oral LD50 value of Modified Small Vinyl Ester in Wistar rats was established to exceed 2000 mg/kg bw. According to the OECD test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg bw.

Acute inhalation exposure study of Modified Small Vinyl Ester is waived on the basis that the substance has a very low vapour pressure as estimated by QSAR (US-EPA EPIsuite v4.0, cf. IUCLID section 13, assessment reports.001). Various constituents amounting to 99% all have vapour pressures below 2E-10 Pa. The residual monomer methacrylic acid (< 0.5 % of Modified Small Vinyl Ester) has a vapour pressure of 132 Pa. Thus, it is evaluated that inhalation of vapours from Modified Small Vinyl Ester in significant amounts is unlikely. Furthermore, Modified Small Vinyl Ester is placed on the market as an approximately 50% solution in a

reactive diluent for industrial use only.

In spray applications, the aerosol size is larger than 65 µm, cf. the measurement of particle sizes under typical spray conditions (attachment to Section 7.2.2). Thus, inhalation of aerosols is unlikely, i.e. Modified Small Vinyl Ester will not be systemically bioavailable by inhalation. Furthermore, respirators are prescribed for work processes that generate aerosols.

Acute dermal toxicity testing is waived on the basis that QSAR estimations (US-EPA DERMWIN v2.01) show that extremely small amounts of the constituents may enter into the body through the naked skin. Based on the dermal absorption of various constituents amounting to 99% of Modified Small Vinyl Ester, the overall relative dermal penetration was calculated to less than 0.00014%, cf. IUCLID section 7.1.2. Thus, taken together with the low toxicity by the oral route, it is foreseeable that the results of acute dermal toxicity testing of Modified Small Vinyl Ester will find a LD50 is much larger than 2,000 mg/kg bw. Modified Small Vinyl Ester is placed on the market as an approximately 50% solution in a reactive diluent for industrial use only. Use of personal protection equipment is required to avoid the possible skin exposure to the marketed solution of Modified Small Vinyl Ester in reactive diluent.

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

Justification for classification or non-classification

The acute oral toxicity of Modified Small Vinyl Ester was determined to be LD50 > 5,000 mg/kg bw in a reliable guideline study. Based on the acute oral results and very low predicted dermal absorption, it is predicted that the acute dermal toxicity would be very low ie LD50 much larger than 2,000 mg/kg bw. The vapour pressure of the constituents was estimated to be low and the particle size of aerosols has been shown to be too large to be inhaled. Thus, inhalation of Modified Small Vinyl Ester is negligible and testing of acute inhalation toxicity was waived. On the basis of this data there is no justification for classification.