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Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
4 263 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute oral toxicity study was conducted according to OECD TG 423 (Acute Toxic Class Method) with 6 female rats (3 per step), receiving each a single dose of 2000 mg/kg of the test item formulated in Kolliphor HS 15/Ethanol/tap water (40/10/50). No mortalities, no effects on body weight gain and no gross pathological findings were observed in the course of the study. Clinical signs (decreased motility, increased salivation, and breathing sounds) were observed only in one animal. The LD50 for the substance is > 2000 mg/kg bw.

 

Further available is a study on the acute inhalation toxicity of the substance, conducted according to OECD TG 403 and OECD GD 39. In this study male and female rats were nose-only exposed to the liquid aerosol of the substance (vehicle: ethanol) at the maximal technical attainable concentration of 4263 mg/m³. The respirability of the aerosol was adequate and in compliance with test guidelines (MMAD 1.14 µm, GSD 2.63). Rats of the control group were exposed to the vehicle ethanol under otherwise identical circumstances.

In this study all rats showed clinical signs (bradypnea, dyspnea, labored breathing, breathing sounds, motility reduced, atony, high-legged gait, piloerection, haircoat ungroomed, nasal discharge (serous), nose reddened, nose/muzzle red encrusted, stridor, nostrils with red encrustation, tremor, salivation increased). Significantly decreased body temperatures and body weights were also found. One animal died; the mortality patterns were typical of a lung edema. Necropsy findings were unremarkable in surviving rats.

The LC50 (4 h) was thus concluded to be > 4263 mg/m³.

 

No study on acute dermal toxicity is available for the substance. However, an assessment on the acute dermal toxicity is possible based on the weight of evidences:

The substance consists to approx. 95 % of four constituents with molecular weights in the range of 105 up to 463 g/mol. Therefore, systemic availability after dermal exposure at least for the lower molecular weight constituents can be anticipated. In fact, the available toxicokinetic data for two of the constituentss, 2,2'-iminodiethanol (DEA; CAS No 111-42-2) and 2,2 -bis(4 -hydroxyphenyl)propane (BPA; CAS No 80-05-7) confirm limited absorption after dermal application (cp. chapter Toxicokinetics).

As summarized above, the available data reveal low toxicity after acute oral exposure with an LD50 > 2000 mg/kg bw. Acute inhalation of the maximum technical attainable concentrations led to changes suggestive of a slight irritant effect to the respiratory tract. An LC50 (4 h) > 4263 mg/m³ was obtained. The available data on irritation/corrosion confirm an irritant property for the substance. Despite the irritant effect which may diminish the protective function of the epidermis (worst case assumption) it is not expected that systemic availability after dermal penetration is higher than after oral exposure. However, in case of the component BPA this has to be seen in relative terms, since an extensive first pass effect decreases systemic availability after oral exposure (cp. EU Risk Assessment Report 2003/2008). Nevertheless, acute dermal toxicity for BPA itself is assessed as low (cp. EU Risk Assessment Report 2003/2008).

With regard to the constituent DEA also a low acute dermal toxicity is reported (cp. OECD SIDS 2007).

In conclusion, with the low toxicity revealed for the substance after acute oral and inhalation exposure and the low acute dermal toxicity for two of the substance's constituents it is not expected that testing on acute dermal toxicity would reveal adverse systemic effects. Local effects that may occur are already assessed by the respective skin irritation/corrosion data. Thus, based on the weight of evidence a conclusion can be drawn that for acute dermal toxicity no hazard is expected. This is in line with recent publications [1][2], in which the benefit of performing acute dermal toxicity studies is in general questioned, in particular if there are no indications for a substance to be hazardous via the oral route. The European Competent Authorities for REACH and CLP (Caracal) have already acknowledged that. From publicly available information it can be derived that the committee agreed on proposals to amend REACH Annex VIII (8.5.3) as such that substances with no acute oral toxicity up to 2000 mg/kg would not require acute dermal toxicity data.[3][4]

[1] Moore, Regulatory Toxicology and Pharmacology, 2013, 66, 30-37

[2] Creton, St. et al, Critical reviews in Toxicology, 2010, Vol. 40 No.1, pages 50-83

[3] http://www.piscltd.org.uk/wp-content/uploads/2014/09/20140714-110033_CA_61_2014-Acute-toxicity-testing-proposal.pdf

[4] https://chemicalwatch.com/20557/caracal-agrees-need-to-drop-acute-dermal-toxicity-tests



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

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

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, no classification is warranted for acute oral toxicity.

With the low toxicity revealed for the substance after acute oral and inhalation exposure and the low acute dermal toxicity for two of the substance's components (BPA and DEA) it can be concluded that data on acute dermal toxicity would not lead to a hazard classification for the substance. Therefore, the available data are considered conclusive for non-classification.

Furthermore, no classification is warranted for acute inhalation toxicity. Although the maximum concentration tested (4263 mg/m³) is below the limit for non-classification according to Regulation (EC) No 1272/2008, Annex I, which is 5000 mg/m³, a classification as Cat. 4 for acute inhalation toxicity is not appropriate due to the following reasons: 1) The maximum concentration tested is the maximal technical attainable concentration that can be achieved for the substance; exposure to a higher concentration than 4263 mg/m³ are not expected to occur. 2) One out of ten animals (5 males, 5 females) died at the concentration of 4263 mg/m³ with mortality pattern typical of a lung edema. Clinical signs in the study (e.g. dyspnoea, serous nasal discharge, red encrusted nose/muzzle, signs of reduced general condition) could be related to respiratory tract irritancy and were proven to be reversible for the surviving animals at the end of the 14 -days observation period. It is not expected that an approx. 17 % higher concentration would lead to a 50 % mortality rate, therefore a classification would not be warranted. 3) Based on the classification of one component that is contained at about 15 % in the substance and in accordance to the signs of respiratory irritation observed in the acute inhalation toxicity study a classification as STOT SE3 is proposed. This classification addresses the toxicological mode of action more adequately than a classification for acute inhalation toxicity.