Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The registration of the test material employs a combined approach for addressing the required endpoints. When data are not available, data from the read across substances are used to address the required endpoints.

 

The read across substances are structurally similar to registered substance. The substance and the proposed structural analogues are predominantly C32 – C36 alkyl fatty amides. These substances are expected to be metabolised by fatty acid amide hydrolase and esterases. Any differences among the substance structures are not expected to result in any significant differences in the toxicological effects or degradation products.

 

The following endpoints include supporting studies to provide evidence of read across suitability:

 

  • Acute toxicity (dermal route);

 

  • In vivo skin irritation;

 

  • In vitro gene mutation study in bacterial cells;

 

  • In vitro cytogenicity study in mammalian cells;

 

  • In vitro gene mutation study in mammalian cells; and

 

  • Repeated dose toxicity study (90 day).

Toxicokinetics

Toxicokinetics

Based upon the physico-chemicals and toxicological properties of the test material and the read across substance there is no / low bioaccumulation potential.

 

Acute Toxicity

Oral route:

In an OECD 420 test guideline, conducted according to GLP conditions, the acute oral toxicity (LD50) of the test material to female Wistar rats is greater than 2,000 mg/kg bodyweight.

 

Inhalation route:

The study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. This endpoint is waived.

 

Dermal route:

In an OECD 402 test guideline study, conducted according to GLP, the acute dermal toxicity (LD50) of the structually similar read across substance to rats is greater than 2,000 mg/kg bodyweight.

 

Irritation

Skin:

Key Study:

In an OECD 439 study, conducted according to GLP, the relative mean viability of the test material with the treated tissues (using the EPISKIN system, in vitro) was 109.2% after a 15-Minute exposure, therefore, is considered not irritating to skin.

 

Supporting Study:

In an OECD 404 study, conducted according to GLP, the read across substances are considered not irritating to skin.

 

Eye

Key Study:

In an OECD 405 study, conducted according to GLP, the test material produced a maximum mean score of 2 after 24 hours in male rabbits (fully reversible after 48 hours), and therefore is considered not irritating to the eye.

 

Supporting Study:

In an OECD 437 study, conducted according to GLP, the ocular irritancy potential of the test material, to the isolated bovine cornea induced an in vitro Irritancy Score of 1.1, and is considered not irritating to the eye.

 

Sensitisation

Skin sensitisation

In an OECD 429 study, conducted according to GLP, the Stimulation Index (SI) of the test material at concentrations of 2.5%, 5% and 10% w/w, are 1.89, 1.36, and 1.16 respectively. The test material is, therefore, considered a non-sensitizer to the skin.

 

Repeat Dose Toxicity

Oral route:

In an OECD 408 study, conducted according to GLP, the sub-chronic toxicity of the structurally similar read across substance in male and female Wistar rats a NOAEL of greater than or equal to 1,000 mg/kg/d was determined. The lack of test item related changes in the reproductive organs, accessory sexual organs, pituitary, adrenal gland, and thyroid provides evidence that the substance lacks the potential to cause reproductive toxicity and no treatment-related histopathological, haematological or clinical effects were observed.

Inhalation route:

A short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solven and route of administration. This endpoint is waived.

Dermal route:

A short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solven and route of administration. This endpoint is waived.

 

Genotixicity

Bacterial gene mutation:

Key Study:

In an OECD 471 study, conducted according to GLP, the test material is non-mutagenic (negative) to Salmonella typhimurium and Escherichia coli bacterial strains.

Supporting Study:

In an OECD 471 study, conducted according to GLP, the structurally similar read across substance is non-mutagenic to Salmonella typhimurium bacterial cells.

 

Cytogenicity:

Key Study:

In an OECD 473 study, conducted according to GLP, the structurally similar read across substance is non-clastogenic to human lymphocytes.

Supporting Study:

In an OECD 473 study, conducted according to GLP, the structurally similar read across substance  is non-mutagenic to rat lymphocytes.

 

Gene mutation in mammalian cells:

In an OECD 476 study, conducted according to GLP, the structurally similar read across substance is non-mutagenic to mouse lymphoma.

 

Reproductive Toxicity

In an OECD 408 study, conducted according to GLP (90-day repeat dose toxicity study) on the read across substance the lack of test material related changes in the reproductive organs, accessory sexual organs, pituitary, adrenal gland, and thyroid provides evidence that the substance lacks the potential to cause reproductive toxicity. The OECD 408 study (90-day study) on a structually similar read-across substance is well conducted and considered reliable. According to Article 25 of Regulation (EC) 1907/2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), and in an effort to reduce the testing burden, and reduce vertebrate testing, vertebrate testing should be undertaken only as a last resort. Given this, and the lack of potential for reproductive toxicity based upon the OECD 408 study (90-day) on the read across substance, the reproductive toxicity endpoint is waived.

 

Developmental Toxicity

In an OECD 414 Prenatal Toxicity study, conducted according to GLP, the maternal and embryo-fetal No-Observed-Adverse-Effect-Level (NOAEL) the test material was considered to be 330 mg/kg/day.  The maternal NOAEL was considered to be 330 mg/kg/day based on the mortality and low body weight gains in rats receiving 1000 mg/kg/day; and the embryo-fetal NOAEL, although no effect on embryo-development was established, was considered to be 330 mg/kg/day - being dependent on maternal toxicity.