Registration Dossier

Administrative data

Description of key information

Not toxic by the oral and dermal routes

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1984-09-28 to 1984-10-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Complete guideline conform study report available. Study is performed under GLP.
Justification for type of information:
The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration Pentamid™ KH (EC 934-047-1). The hypothesis is that data can be read-across between Pentamid™ KH and its structural analogues, based on structural similarity and common breakdown/metabolic products (Scenario 1 of the Read-Across Assessment Framework (RAAF, ECHA, 2015)).

For mammalian toxicity the “parent” substances show no significant systemic or dermal toxicity in mammals and vertebrates. One of the metabolic products of Pentamid™ KH, the well-studied terephthalic acid, has no significant systemic toxicity. The amine metabolite, however, shows diffuse mammalian systemic toxicity at moderate concentrations. This metabolite is employed in the risk assessment, in agreement with the European Union draft Risk Assessment Report of 2008.

The sole classification for Pentamid™ KH is the precautionary aquatic chronic 4 category, based on low water solubility and a log Kow higher than 4.

Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Doses:
single dose: 5000 mg/kg bw
No. of animals per sex per dose:
5 /sex/group
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the 14 day observation period
Clinical signs:
Immediate after application of the test substance the following signs of toxicity were observed: Hypoactivity, crouch and scrubby fur. The day after treatment no signs of toxicity were observed.
Body weight:
No effect on body weight were observed.
Gross pathology:
No macroscopic visible effects were observed.
Other findings:
No other findings.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the acute oral toxicity study of a structural analogue source material, the median lethal dose (LD50) of this test substance after single oral administration to male and female Wistar rats observed over a period of 14 days is over 5000 mg/kg bw. The target substance is not calssified for acute oral toxicity according to Regulation EC No. 1272/2008.
Executive summary:

A study was performed to determine the acute oral median lethal dose (LD50) of the source

material, administered once per oral gavage as a solution in 12.5% sesame oil in Wistar rat. The

method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No.

401 "Acute Oral Toxicity" referenced as EU Method B.1 (Acute Toxicity (Oral)).

Ten fasted animals (five per sex) were given a single oral dose of test material at the dose level of

5000 mg/kg bw. No mortality occurred. Immediate after application of the test substance the

following signs of toxicity as hypoactivity, crouch and scrubby fur were observed. No clinical

signs were observed the day after the treatment and during the observation period of 14 days. No

effect on body weight development was observed. At the end of the observation period all rats

were sacrificed with CO2 gas. Gross pathological examination dit not reveal any alteration.

Based on the results of above mentioned study the median lethal dose (LD50) of the source

substance after single oral administration to male and female rats, observed over a period of 14

days is over 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
adequate

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
If no dermal tox study exists and is waived: According to Annex VIII, Section 8.5, Column 2, of Regulation EC No. 1907/2006, a toxicity study, in addition to the acute oral toxicity study, under 8.5.2 to 8.5.3 shall be provided for at least one other route. Commission Regulation (EU) 2016/863 amends this data requirement, stating that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. The risk of acute toxicity by the dermal route has been addressed in light of an acute oral toxicity study with a LD50 > 2000 and no systemic toxicity observed in other in vivo studies. It is determined that testing for acute dermal toxicity is not scientifically indicated. The criteria for satisfaction of Sections 8.5.2 and 8.5.3 are met and the data requirement for an acute toxicity study by a third route, inhalation, is waived.
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
Justification for type of information:
According to Commission Regulation (EU) 2016/863 amending Regulation EC No. 1907/2006, acute testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route, and no systemic effects have been observed in in vivo studies with dermal exposure. The test material displayed an acute oral LD50 > 2000 mg/kg bw in rats, is not classified as STOT SE, and no systemic toxicity or local irritation was observed in dermal studies. Therefore the substance meets the criteria for waiving the testing requirements for acute dermal toxicity.
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The acute oral toxicity to rats of a close structural analogue substance is > 5000 mg/kg bw. Commission Regulation (EU) 2016/863 amends the Annex VIII, Section 8.5 requirement for toxicity data on two routes of administration, stating that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. The risk of acute toxicity by the dermal route has been addressed in light of an acute oral toxicity study with a LD50 > 2000 and no systemic toxicity observed in other in vivo studies. The criteria for classification for acute toxicity for any route of administration are not met.