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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-01-07 to 2015-01-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Based on OECD test guideline and GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)"
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000), including the most recent revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(1S)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propanol
EC Number:
608-251-3
Cas Number:
287930-77-2
Molecular formula:
C29H28NO2Cl
IUPAC Name:
(1S)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propanol
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Appearance: White powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species Rat, Wistar strain, Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.

Number of animals: 5 males and 5 females (females were nulliparous and non-pregnant).
Age and body weight: Young adult animals (approx. 10 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.

Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Accommodation
Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).

Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).

Water
Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.

Administration / exposure

Type of coverage:
open
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% Aqueous carboxymethyl Not indicated cellulose
Details on dermal exposure:
The formulation was applied on an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).
Duration of exposure:
24 hours, after which dressings were removed and the skin cleaned of residual test substance using tap water.
Doses:
2000 mg/kg (10 mL/kg) body weight.
No. of animals per sex per dose:
5/sex/group
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were subjected to daily observations and weekly determination of body weight. Mortality/viability was observed twice daily. Animals were weighed on days 1 (pre-administration), 8 and 15. Clinical signs were observed at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Terminal sacrifice was performed on day 15

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Lethargy, flat posture, hunched posture, piloerection, chromodacryorrhoea (snout) and/or ptosis were noted for the animals on Day 1. White staining and/or scales were seen in the treated skin-area of the animals between Days 2 and 11.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of Montelukast Backbone Diol in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Montelukast Backbone Diol does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).