Registration Dossier

Toxicological information

Additional toxicological data

Currently viewing:

Administrative data

Endpoint:
additional toxicological information
Type of information:
other: expert statement
Adequacy of study:
other information
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The TKA was conducted in accordance with Annex VIII Section 8.8 of Regulation (EC) No. 1907/2006, also known as REACH. The TKA is also based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2008)5. The assessment of toxicokinetic behavior was based on available data and information provided by the client and found in a search of the published literature using PubMed and Google. No additional specific studies were conducted for the purposes of developing the TKA.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
The TKA was conducted in accordance with Annex VIII Section 8.8 of Regulation (EC) No. 1907/2006, also known as REACH. The TKA is also based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2008)5. The assessment of toxicokinetic behavior was based on available data and information provided by the client and found in a search of the published literature using PubMed and Google. No additional specific studies were conducted for the purposes of developing the TKA.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no details, since a category of substances is described.

Results and discussion

Any other information on results incl. tables

1.       TOXICOKINETIC BEHAVIOR

1.1   Absorption

Nonionic surfactants are known to be useful promoters of drug absorption from the gastrointestinal tract3. The primary basis for improved GI absorption are surfactant effects on drug solubility, dissolution, emulsification, micellar solubilization and gastric emptying3. Some nonionic surfactants are known to promote drug absorption by a direct effect on gastric membranes3. The electrical neutrality on nonionic surfactants generally make them less toxic and nonionic surfactants possess relatively less direct toxicity than cationic or anionic surfactants to gastrointestinal mucosa3. Members of the AGDS category are not acutely toxic by the oral route in the rat, the dermal route in rabbits or by inhalation in rats. The lack of systemic toxicity in 28-day repeat dose toxicity studies in rats by the oral route is a further indication of a lack of absorption and toxicity through the gastrointestinal tract.

 

The low vapor pressure exerted is an indication of low potential exposure by the inhalation route as well. Surfactants in general are known to have a direct irritant effect on the mucous membranes of the eyes and the upper respiratory tract.

 

It has been generally shown when using surfactants in cosmetics that percutaneous absorption of nonionic surfactants is greater than that for anionic or cationic surfactants4. The rate of skin absorption of nonionic surfactants decreases with increasing levels of ethoxylation4. Nonionic surfactants tend not to interact with proteins in the skin4. It is likely that Surfynol 400 and Surfynol 2502 will have even less dermal absorption than the other members of the AGDS category. None of the members of the category were shown to be toxic by the dermal route however which supports that the conclusion that dermal absorption is relatively low for all members of the class. It is also possible that substantial damage to or removal of the epidermal layer of the skin would enhance dermal absorption of the members of the AGDS category.

 

 

1.2   Distribution

No evidence of systemic target organ toxicity was seen in repeat dose studies in the rat given members of the AGDS category by the oral route1. Toxicity seen in the liver at the highest dose tested is likely the result of compensatory responses to high doses administered however it is also an indication of some minor distribution of the compounds to highly perfused tissues such as the liver. Based on the relatively high degree of water solubility it is unlikely that members of the AGDS category will accumulate in body fats and/or breast milk.

 

Direct effects of nonionic surfactants are of greater importance than systemic effects. The lack of evidence of vomiting and diarrhea is evidence that there is no direct damage to the mucous membranes of the GI tract. Inhalation of nonionic surfactants may also be disruptive to pulmonary function due to direct interaction of the surfactant with surface-active film lining the airways4.

 

1.3   Metabolism

Genotoxicity testing with each member of the AGDS chemical category indicates that each of the compounds is non-mutagenic and non-clastogenic in tests conductedin vitroboth with and without the presence of an S9 metabolic activation system isolated from rat liver. In each assay metabolism by S9 rat liver enzymes did not result in increased mutation frequency.

 

In the environment, all members of the category display stability in water. The group shows a lack of ready biodegradability but may be inherently/ultimately biodegradable1. Category members show a moderate tendency to adsorb to organic carbon, typical of surfactants1. 

 

1.4   Elimination

Fecal excretion is likely the major route of elimination of unabsorbed and unchanged compounds in the AGDS category. Some nonionic surfactants are known to be resorbed in the large intestine4although this has not been specifically shown for any member of the AGDS category. If resorption occurs some elimination of the compound in bile is possible.

 

None of the members of the AGDS category are systemically toxic by the oral, dermal or inhalation routes in animal studies. Data suggests low potential for absorption across the skin, gastrointestinal tract and respiratory tract but suggests the possibility of direct irritant effects on the mucous membranes of the eyes and upper respiratory tract. It is likely significant absorption, distribution and metabolism occurs. Elimination is likely via the fecal route.

Applicant's summary and conclusion

Conclusions:
None of the members of the AGDS category are systemically toxic by the oral, dermal or inhalation routes in animal studies. Data suggests low potential for absorption across the skin, gastrointestinal tract and respiratory tract but suggests the possibility of direct irritant effects on the mucous membranes of the eyes and upper respiratory tract. It is likely significant absorption, distribution and metabolism occurs. Elimination is likely via the fecal route.