Germanium tetrachloride

Endpoint summary

Description of key information

Acute rat inhalation test (Terrill et al., 1990, Hazleton laboratories) (KL=2):
A single one-hour (3.3g/m³) whole body exposure resulted in severe toxic effects. 
By vapour exposure, GeCl4 was unique in that the injury of tissue (necrosis) 
was markedly greater for the skin than for the respiratory tract. 
Due to the corrosive nature of the test material and the clinical signs 
displayed by the animals, all animals were sacrificed for humane reasons on test day 4. The exposure concentration 3.3g/m³
needs to be considered as an LC100 (1h) 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented , although only 1 concentration tested and 1h exposure, meets generally accepted scientific principles, acceptable for assessment.

Principles of method if other than guideline:

A single one-hour (3.3g/m³) whole body exposure

GLP compliance:

yes (incl. QA statement)

Test type:

other: A single one-hour whole body exposure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina
- Age at study initiation: 49 weeks
- Weight at study initiation: male: 232.6-269.0 g; female: 200.0-209.1 g
- Fasting period before study: no information
- Housing: individually housed in elevated, stainless-steel, wire-mesh cages
- Diet: Purina certified rodent laboratory chow 5002 ad libitum
- Water: Tap water ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 25°C
- Humidity (%): 43-60
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12hrs dark /12 hrs light

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A Razel syringe pump (Model A-99) was used to pump the liquid test material, contained in a 10ml Hamilton glass and Teflon syringe, to an atomizer for generation of the vapor. Compressed air was metered to the atomizer through a 0-40Lpm Dwyer flowmeter and a backpressure gauge. The resultant vapor-laden airstream was directed from the atomizer to the inlet of the exposure chamber.
- Exposure chamber volume: 100-liter plexiglass exposure chamber
- Temperature, humidity, pressure in air chamber: continuously monitored during the exposure

TEST ATMOSPHERE
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 h

Concentrations:

379ppm (conversion factor of 114.3 = 1mg/L) = 3.315g/m3

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 4days
- Frequency of observations and weighing: prior to exposure (day1) and at terminal sacrifice (day4)
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

Calculation of time-weighted-average (TWA) exposure levels were performed using a program developed and validated by Hazleton laboratories America, Inc.

Sex:

male/female

Dose descriptor:

other: EC100

Effect level:

3 315 mg/m³ air

Based on:

test mat.

Exp. duration:

1 h

Remarks on result:

other: necrotic paw(s) and/or nose, rough haircoat, opaque or squinted eye(s), swollen paw(s), few or no feces, pale ears and eyes, urine stains, increased secretory responses, respiratory distress , languid behavior and loss of body weight

Mortality:

Due to the corrosive nature of the test material and the clinical signs displayed by the animals, all animals were sacrificed for humane reasons on test day 4

Clinical signs:

other: -languid behavior, squinted eyes, dyspnea, opaque eyes, urine stains, wheezing and red or green colored crusts were exhibited by the animals during exposure or at the 30 or 60 minutes post-exposure period -clinical signs observed during the test day 2-4 p

Body weight:

almost all animals showed a weight loss on test day 4 compared to their pretest body weight

Gross pathology:

swollen, necrotic, and/or sores on the paw(s), necrotic skin, eschar on the skin, pale kidney, pale eye, opaque external eye, raised area on the external eye, pale spleen, mottled lung and dark nasal turbinate

Other findings:

none

none

Interpretation of results:

other: substance is extremely corrosive

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

By vapor exposure, this material was unique in that the injury of tissue (necrosis) was markedly greater for the skin than for the respiratory tract.
Due to the complete hydrolysis of the substance with formation of HCl, the respiratory effects and classification are based on those of HCl (STOT SE 3)

Executive summary:

One group of 5 male and 5 female Sprague-Dawley rats received a single one-hour whole-body exposure to germanium tetrachloride as a vapor at an analytical concentration of approximately 379 parts per million (v/v, in air). Clinical signs associated with treatment included necrotic paw(s) and/or nose, rough haircoat, opaque or squinted eye(s), swollen paw(s), few or no feces, pale ears and eyes, urine stains, increased secretory responses, respiratory distress , languid behavior and loss of body weight. Due to the extemely poor physical condition of the animals, they were sacrificed for humane reasons on test day 4 instead of test day 14. Gross postmortem examinations of sacrificed animals revealed swollen, necrotic, and/or sores on the paw(s), necrotic skin, eschar on the skin, pale kidney, pale eye, opaque external eye, raised area on the external eye, pale spleen, mottled lung and dark nasal turbinate.

It was concluded that, by vapor exposure, this material was unique in that the injury of tissue (necrosis) was markedly greater for the skin than for the respiratory tract.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

GeCl₄is a data-poor substance. However, a relatively large amount of toxicity data is available for GeO₂. Since GeCl₄readily hydrolyses (even with the humidity in the air) to form GeO₂and HCl, the applicability of using GeO₂toxicity data to read across to GeCl₄was evaluated.

In order to make a straightforward comparison possible between available data on GeCl4 and GeO2,the effect concentrations reported for GeCl₄were converted to their GeO₂equivalents (i. e. effects concentrations are corrected for molecular weight). 

Acute toxicity: oral:

No reliable acute oral toxicity data was available for GeCl₄. In order to enable comparison with the available GeO₂data, the acute inhalation EC₁₀₀for GeCl₄was converted to an oral ED₁₀₀using route-to-route extrapolation (allometric scaling principle-ECHA guidance R8) (cfr table below).

It can be concluded that the available lethal concentrations for GeO₂are higher than the lethal concentrations for GeCl₄.

Acute toxicity: inhalation:

The reported acute inhalation LC₅₀for GeO₂is > 3.1g/m³ whereas the normalized EC₁₀₀forGeCl₄to equivalent GeO2 is 1.6g/m³. A direct comparison between similar effect concentrations is impossible (i.e. LC₅₀versus EC₁₀₀), however it can be concluded that the lethal concentrations for GeO₂are higher than the lethal concentrations for GeCl₄ (cfr table below).

Table: Overview of available acute toxicity data on GeCl4 and GeO2 and overview of the conversion of GeCl4 effect data to GeO2 equivalents(based on molecular weight).

 

* route to route extrapolation: 3,316mg/L x 0,8L/min/kg x 60min ==> LD100 = 159mg/kg (allometric scaling principle - Echa guidance R8) conc

	Reference	Klimisch	Exposure range			Duration	Effectconc	Qualifier	Normalization to equivalent GeO2 Exposure range         Effect
GeCl4	acute inhal (Terrill et al., 1990, Hazleton laboratories)	2	3.316	/	g/m3	1h	3.316g/m3	EC100	1.632           /	1.632g/m3
	data extrapolated to 4h standard					4h	0.829g/m3	EC100		0.408g/m3
	route-to-route extrapolation*						0.159g/kg	ED100		0.078g/kg
GeO2	acute inhal (Arts et al., 1994)	2	3.1	/	g/m3	4h	>3.1g/m3	LC50	lethal conc GeO2 > GeCl4 lethal conc GeO2 > GeCl4 lethal conc GeO2 > GeCl4
			1.42	/	g/m3	4h	>1.42g/m3	LC50
	acute oral (Faroon et al., 2007)	3	/	/	g/kg	NI	3.7g/kg	LD50
	acute oral (Faroon et al. , 2007)	3	/	/	g/kg	NI	6.3g/kg	LD50

Valid to read across based on GeO₂data?

Based on this exercise it was envisaged to evaluate whether a read across from GeO₂-induced systemic effects would be valid for GeCl_4.The answer to this question is clearly negative. Corrosive effects of GeCl₄(attributable to hydrolysis with formation of HCl ) will occur at much lower concentration and before other potential GeO₂-induced effects can be induced.

Because of the high corrosive potential of GeCl₄at relatively low concentrations, it was concluded that read across based of GeO₂toxicity data is not relevant. Severe corrosive effects of GeCl₄will occur before systemic effects triggered by GeO₂can be initiated.

Justification for classification or non-classification

Specific target organ toxicity — single exposure:

Due to the complete hydrolysis of the substance with formation of HCl, the respiratory effects and classification are based on those of HCl (STOT SE 3)