Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity - Fixed Dose Method OECD Guideline 420, limit dose: LD50 > 2000 mg/kg b
(Acute Inhalation Toxicity) (OECD Guideline 403), modified: whole-body, 5M/5F, one dose of 5 mg/l (vapour): LC50 > 5 mg/l

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
5 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

HD4 did not show any evidence of toxicity, barring some slightly ruffled fur, at a dose level of 2000 mg/kg body weight after single oral administration to six female rats, observed over a period of 14 days (Reconsile, 2010a).

The key acute inhalation study was performed using a mixture of the registered substance and 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5). There were no mortalities, clinical signs or adverse necropsy findings following 4-hour exposure at a limit dose of 5 mg/l (Dow Corning Corporation, 2002a).

Read-across justification

Read-across to the submission substance is justified because: (i) the test substance includes ca.50% by weight of the submission substance, (ii) as the submission substance has a higher vapour pressure (479 Pa) than the other component (0.1 Pa) the effects of the submission substance are expected to dominate, and (iii) the second component is a close structural analogue of the submission substance.

In addition, HD4 is one of a number of cyclic siloxanes containing no functional groups for which acute toxicity data are available. The results of all available studies, summarised in the table below, are in agreement and show that none of the substances in this analogue group is acutely harmful by any exposure route.

Acute toxicity data for cyclic siloxanes

CAS Number

556-67-2

2370-88-9

541-02-6

6166-86-5

540-97-6

Name

Octamethylcyclotetrasiloxane

2,4,6,8-tetramethylcyclotetrasiloxane

 

Decamethylcyclopentasiloxane

2,4,6,8,10-pentamethylcyclopentasiloxane

 

Dodecamethylcyclohexasiloxane

Synonym

D4

HD4

D5

HD5

D6

Acute oral toxicity LD50(mg/kg bw)

>4800

(Löser, 1979)

>2000

(Reconsile, 2010a)

>5000

(Toxikon, 1990a)

>2000

(Reconsile, 2010b)

>2000

(Notox, 1999a)

Acute dermal toxicity LD50(mg/kg bw)

>2400

(Ramm, 1985)

-

>2000

(WIL, 1977)

-

>2000

(Notox, 1999b)

Acute inhalation toxicity LC50(mg/l)

36 mg/l

(Dow Corning Corporation, 1994)

-

8.7 mg/l

(RCC, 1994)

-

-



Justification for selection of acute toxicity – oral endpoint
The selected study is the only available acute oral toxicity for the registered substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for selection of acute toxicity – inhalation endpoint
The selected study is the only available acute oral toxicity for an appropriate surrogate substance. It was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.

Justification for classification or non-classification

Acute toxicity, oral:

LD50 (female rat): greater than 2000 mg/kg body weight

Based upon the classification criteria in Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, 2,4,6,8 -Tetramethylcyclotetrasiloxane is not classified with respect to acute oral toxicity in the rat.

Acute toxicity, Inhalation: LC50, rat > 5 mg/l

The selected single dose is in the range of 2 <ATE <= 10 mg/l or Categoy 3 according to CPL regulation (EC) No 1272/2008.

However, given the absence of any toxic effect at 5 mg/l as well as in the acute irritation/ corrosion studies and the absence of acute toxicity studies at a higher dose level, the data for inhalation are considered inconclusive and no classification is proposed. The lack of classification is supported by the results of the range finding study for the ongoing 28-day repeated dose inhalation toxicity study. No mortalities were observed at 1000 ppm (9.8 mg/l); onemale animal (out of 5 animals) in the 4000 ppm (39 mg/l) group was killed in extremis and there was one female (out of 5 animals) spontaneous death in this dose group.