Reaction mass of Fatty acids, montan-wax and Fatty acids, montan-wax, ethylene esters and Fatty acids, montan wax, mixed esters with fatty acids C16-18 and ethylene glycol and Fatty acids, montan-wax, stearyl esters and Montan wax

Endpoint summary

Description of key information

No toxic effects were observed in any of the available repeated oral dose studies with different types of Montan waxes up to the highest doses tested (study reliability RL1 or RL2). This finding is supported by reliable studies with structurally related substances from plant origin. Information on inhalation and dermal exposure is not available, but these exposure routes are not considered to be of concern.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.

Reason / purpose for cross-reference:

assessment report

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related adverse effects were observed

Remarks on result:

other: Montan wax, type S

Critical effects observed:

no

Conclusions:

Under the conditions of this oral combined repeated dose and reproduction / developmental screening study according to OECD 422 and GLP, no treatment-related effects were observed up to 1000 mg/kg bw/day, the highest dose tested.

Executive summary:

The study used as source investigated oral short term toxicity in rats. The study results of the source compound were considered applicable to the target compound and were used for classification and labelling acc. to REGULATION (EC) No 1272/2008. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in section 13 or find a link in cross reference “assessment report”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

reliable studies (klimisch score 1 or 2) for members of the montan wax category and structurally related substances are available

System:

other: no treatment-related adverse effects were observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral exposure

Montan waxes, type WE4 was tested in a reliable 90-days study with rats (RL2). No adverse effects could be observed in any of the exposure groups. The highest dietary concentration of 50000 mg/kg diet corresponds to body doses of 3916-4090 mg/kg bw/day.

Rats were exposed to Montan waxes, type KPS in a reliable study (RL2) for 2 years in concentrations up to 5% (50000 mg/kg diet, corresponding to body doses of 2000 and 2500 mg/kg bw/day for females and males, respectively). Animals underwent histological examinations (macroscopy and histopathology: heart, lungs, liver, kidneys, adrenal glands, spleen, pancreas, thyroid gland, pituitary gland, brain and testes/ovaries), further haematological endpoints and urinalysis were performed. No treatment-related effects were observed, resulting in a NOAEL ≥ 2500 mg/kg bw/day. Supporting information comes from a dog study with dietary exposure to Montan waxes, type KPS up to 50000 mg/kg diet (1250 mg/kg bw/day) for 90 days. No adverse effects were evident.

A very poorly reported (RL3) study with subacute exposure of rats observed liver effects (slight fatty degeneration in an unspecified numbers of animals) as well as kidney effects (proteinuria and histopathological alterations in 50% of exposed rats) with Montan waxes, type KPS after exposure to oral body doses of 1000 mg/kg bw/day, given 28-times within 32 days. As the results of the latter study are insufficiently reported and are in contrast to those of the reliable 2-years rat study with the same type of Montan wax (see above) and all other studies (with longer exposure periods) for different types of Montan waxes as well as structurally related substances from plant origin, they are not considered to be relevant for risk assessment.

 

A recent guideline study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test acc. to OECD guideline 422, RL1) with Montan waxes, type S did not observe adverse effects in parental rats up to the highest dose (1000 mg/kg bw/day). In this study, the premating exposure period was expanded to 10 weeks. Due to the effects observed on platelet aggregation in a study with D-003 (see below), this parameter was tested additionally to the usual range of examinations, and no corresponding effects were observed.

 

Supporting information comes from studies with structurally related substances from plant origin:

- A reliable 6-months study (RL2) with oral exposure of rats to D-003 (origin: sugar cane wax; composed predominantly of even-numbered long chain fatty acids, mainly C24-C36 with a maximum of C28-C32) revealed a NOAEL of ≥ 1000 mg/kg bw/day (except blood coagulation and cholesterol levels, a specific effect of this type of acids - which is not shared by the Montan waxes, see above - with a LOAEL of 250 mg/kg bw/day). 1000 mg/kg bw/day was the highest dose tested in this study. The observation of reduced platelet aggregation and reduced cholesterol levels in this study was the reason to test these parameters in the OECD guideline 422 study with Montan waxes, type S (see above).

- Carnauba wax (origin: leaves of tropic palms; composed predominantly of esters of even-numbered long chain fatty acids and alcohols, mainly C14-C34 acids with a maximum of C20-C30, mainly C20-C36 alcohols with a maximum of C30-C34, as well as free aliphatic long chain fatty acids and alcohols, esters of ω-hydroxy-carboxylic acids with mainly C20-C36 alcohols with a maximum of C30-C34, and lower amounts of esters of p-hydroxy- and p-methoxycinnamic acid) was tested in a reliable (RL2) 13 weeks-study on rats. No toxic effects were observed after exposure in diet corresponding to body doses up to 10200 mg/kg bw/day.

Further support comes from reliable long-term studies with structurally related substances (for study details see section carcinogenicity): 

-             D-003: NOAEL 1500 mg/kg bw/day, rat, 2 years (Gamez et al., 2007)

-             Policosanol: NOAEL 500 mg/kg bw/day, rat, 2 years (Aleman et al., 1994)

A significant reduction of platelet aggregation and cholesterol serum values was evident in the subchronic study with D-003, but these are substance-specific effects which could not be observed in studies with Montan waxes: the bleeding time (the functional alteration which would be expected due to a disturbed platelet aggregation) after oral exposure to 1000 mg/kg bw/day Montan waxes, type S was not increased after 4 weeks of exposure (Sisti and Oberto, 2010) and no reduction of blood lipid levels were observed in a subacute study with Montan waxes, type S (Wang et al., 2005, see CSR chapter 5.10). In agreement, no such effects could be observed in a recent extended OECD 422 study with Montan waxes, type S (see above).

No adverse effects were observable at the highest concentration tested in any of the studies, i.e. only NOAELs were derived and the LOAELs after repeated exposure remains unidentified. Supported by the very low acute toxicity it is expected that the true NOAEL is much higher than the NOAEL identified in the studies with repeated oral exposure.

 

Please note that studies for the higher tonnage band (>100 tonnes, corresponding to REACH Annex IX and X) and which are included in the CSR and the IUCLID dossiers (lead registrant) of the respective category members are not reported here.

Inhalation exposure

This information is not available. In accordance with column 2 of REACH Annexes VIII, the repeated dose toxicity study, as required in section 8.6.1 of Annex VIII, does not need to use the inhalation route because exposure of humans via inhalation is considered unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

 

Dermal exposure

This information is not available.In accordance with column 2 of REACH Annexes VIII, the repeated dose toxicity study, as required in section 8.6.1 of Annex VIII, does not need to use the dermal route because

- the physicochemical and toxicological properties do not suggest potential for a significant rate of absorption through the skin,

- the toxicity after acute dermal application is not considered to be higher than that after acute oral administration,

- no systemic effects or other evidence of absorption were observed in skin and eye irritation studies,

- there are no in vitro tests that suggest significant dermal absorption, and

- no significant dermal toxicity or dermal penetration is recognized for structurally related substances.

Justification for classification or non-classification

Based on the findings of several reliable repeated dose toxicity studies the Montan waxes category members have not to be classified for effects of repeated exposure according to Regulation (EC) No 1272/2008.