Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: assessment
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: toxicokinetics assessment was completed according to ECHA Guidance on information requirements and chemical safety assessment, Chapter R.7c, R.7.12 Guidance on Toxicokinetics (November 2012, version 1.1)

Data source

Reference
Reference Type:
other: assessment
Title:
Unnamed
Year:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment, Chapter R.7c, R.7.12 Guidance on Toxicokinetics (November 2012, version 1.1)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: crystal

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Oral absorption: the substance is a moderate molecular compound and is not readily soluble in water. It does not contain hydrolysable groups. Tthe substance as such has a low potential to hydrolyse in the dark. However, as it is a photoinitiator, it would be expected to rapidly degrade in the environment upon exposure to nature light.
Although some unspecific symptoms of intoxication were observed in the acute oral toxicity study (reversible within 10 days in all of the animals), the test result LD50 > 5000 mg/kg bw/day indicated that no signs of systemic toxicity were present. System effects observed in the repeated dose toxicity study (28 day) showed oral absorption took place. Since the substance has low water solubility and relatively large particle size, it is estimated that oral/GI absorption is low.

Respiratory absorption: since the substance has low water solubility, relatively large particle size, low volatility and low vapour pressure, respiratory absorption is anticipated to be low.

Dermal absorption: although some unspecific symptoms of intoxication (reversible within 8 days in all animals) were observed in the acute dermal toxicity study, the test result LD50 > 2000 mg/kg bw/day indicated that no signs of systemic toxicity is present. In skin sensitisation (GPMT) test, erythema was observed in one of the four animals in the pre-test (during 24 h after the occlusive application of 30% of the test substance in Vaseline). Due to limited information, it is difficult to assess further. Thanks to its low vapour pressure and log P value of 2.9, it is anticipated that the substance has dermal absorption. However, the dermal absorption could be low because of its low water solubility.
Details on distribution in tissues:
In both acute oral and dermal toxicity studies, some unspecific symptoms of intoxicaiton were observed, which were reversible within 8-10 days in all animals. System effect such as liver and kidney effects were observed in 28-day oral toxicity study. Based on these observations, the substance could be considered to have transported. Considering its low water solubility and log P value of 2.91, it is estimated that distribution of the substance is low. Not being a lipophilic substance, the substance would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace but may accumulate if exposures are continuous. There is no evidence to indicate substance will accumulate in fat or in other tissues.
Details on excretion:
The 28-day oral toxicity study noted the urine effect as follows: urine analysis revealed an increased number of epithelia in the sediment as well as a slightly increased incidence of reducing substances in the urine in the high-dose group, particularly among the males. These findings were reversible.
In comparison to characteristics favourable for urinary excretion, it is estimated that the urine effect in 28-day oral toxicity study is an adaptable change as a result of excretion of metabolism of the substance.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
No metabolism studies on the substance could be found in the literature.
The 28-day oral toxicity study indicated that in the high-dose group there was a slight anaemia which proved to be completely reversible within the follow-on observation period. In the same dose group some clinico-chemical parameters differed from the control values. Although these changes were not statistically significant, they were assessed as being substance-related. After the end of the follow-on observation period these differences could no longer be measured. Based on the changes above, the substance is expected to be metabolised.

Applicant's summary and conclusion

Conclusions:
System effects which were observed in the repeated dose toxicity study (28 day, oral) showed oral absorption took place. Since the substance has low water solubility and relatively large particle size, it is estimated that oral/GI absorption is low. Respiratory and dermal absorption are anticipated to be low.
There are no metabolism studies available. Based on the changes in blood chemistry and different clinico-chemical parameters in the 28-day oral toxicity study, the substance is expected to be metabolised. Urine effect of excretion for the substance was noted .