Registration Dossier

Administrative data

Description of key information

Proprietary (guideline & GLP-compliant) acute oral, dermal and inhalation studies are available for cthe compounds in this group.  A number of
additional published studies have been reviewed by the UK Health & Safety Executive (HSE, 1989), the UK Institute of Occupational Health (IOH, 1997) and the EU RAR (2005). The EU RAR also covers the studies previously reviewed in the other two reports.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
59 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
200 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Chromium trioxide

Studies show that chromium trioxide is acutely toxic by the oral and dermal routes and is very toxic by inhalation. The primary effects of exposure appear to be corrosion at the site of exposure, however evidence of renal toxicity was also seen in the dermal and inhalation toxicity studies.

The acute oral toxicity of chromium trioxide is slightly higher than that of other water-soluble hexavalent chromium compounds, possibly as a consequence of more severe local corrosive effects due to the low pH of this substance. The acute inhalation toxicity is comparable to that of other water-soluble hexavalent chromium compounds, however the acute dermal toxicity of chromium trioxide is much more severe due to local effects. Read-across between chromium trioxide and the other substances in this group for acute dermal toxicity is therefore inappropriate.

Acute oral toxicity

The results of proprietary acute oral toxicity studies (Loser, 1987; Shults, 1987) are consistent with the results of other studies available in the literature (EU RAR, 2005) and report the lowest acute oral LD50 values (of 52 and 80 mg/kg bw/d respectively) for chromium trioxide. The UK IOH review (1997) also reports the results of a study with chromium trioxide (Kobayashi et al, 1976) which gives acute oral LD50 values of 41 -59 mg Cr /kg bw, which would appear to be broadly consistent with the results of other studies. Chromium trioxide is listed on Annex I of Directive 67/548/EEC as (R25) 'Toxic if swallowed'; this is consistent with the proprietary study and the additional data summarised in the EU RAR and UK IOH reviews and no change to this classification is proposed.

Acute inhalation toxicity

The only available acute inhalation toxicity for chromium trioxide is the proprietary study (Rhinehart, 1989), which reports an LC50 value of 217 mg/m3. The results of this study indicate local irritation/corrosion of the respiratory tract to be the primary cause of immediate death, with some evidence also for delayed mortality due to renal toxicity. Chromium trioxide is listed on Annex I of Directive 67/548/EEC as (R26) 'Very toxic by inhalation'; this is consistent with the proprietary study and no change is proposed.

Acute dermal toxicity

The results of the proprietary acute dermal toxicity study (Shults, 1987) are also discussed in the EU RAR, and in fact are the only data available for this compound. In comparison to the other Cr (VI) compounds, chromium trioxide was found to be of relatively high acute dermal toxicity (LD50 = 57 mg/kg bw). This finding is considered highly likley to be a consequence of the severity of the local dermal effects seen following exposure to this corrosive chemical. It is notable that mortality was also seen in a dermal irritation screening study in rabbits performed with chromium trioxide (Thyssen, 1979) at dose levels equivalent to 125 -170 mg/kg bw. Chromium trioxide is listed on Annex I of Directive 67/548/EEC as (R25) 'Toxic in contact with skin'; this is consistent with the proprietary study and no change to the classification is proposed.

Sodium chromate

Acute oral toxicity

The acute oral LD50 of sodium chromate in the rat was found to be 129.5 mg/kg bw (males) and 67.0 mg/kg bw (females) in a proprietary, guideline-compliant study (Cuthbert & D'Arcy-Burt, 1983). Findings are consistent with those reported in the literature (EU RAR, 2005; UK IOH, 1997) and in an additional guideline-compliant study (Gad et al, 1986) which reported values of 67.08 and 40.57 mg/kg bw in males and females respectively. The UK IOH review also refers to a study by Gad et al (1986) which reported an acute oral LD50 value of 87 mg/kg bw, and may in fact be the same as the proprietray study. Sodium chromate is listed on Annex I of Directive 67/548/EEC and is classified as (R25) 'Toxic if swallowed', which is consistent with the findings of these studies. No change to this classification is proposed.

Acute inhalation toxicity

A proprietary study (Greenough & McDonald) reported 100% mortality for sodium chromate at a concentration of 3.15 mg/l. The results of an additional study (Gad et al, 1986) reported briefly in the UK IOH review (1997) reports an LC50 value of 104 mg/m3. Sodium chromate is listed on Annex I of Directive 67/548/EEC as (R26) 'Very toxic by inhalation'; this is consistent with the proprietary study and no change to this classification is proposed based on the results of this study and the results of a proprietary study performed with potassium dichromate (read-across).

Acute dermal toxicity

The acute dermal LD50 of sodium chromate was found to be >2000 mg/kg bw in a guideline-compliant study in the rabbit (Cuthbert & D'Arcy-Burt, 1983). The findings of this study contrast with the results of an additional guideline-compliant study (Gad et al, 1986) using the same application conditions, in which a dermal LD50 of 1330 mg/kg bw was determined for male rabbits. Signs of systemic toxicity were noted in a skin irritation study in the rabbit (Cuthbert & D'Arcy-Burt, 1982); the level of mortality in this study indicates a dermal LD50 of <250 mg/kg bw, however findings may be due to the use of a vehicle in this study which increased the bioavailability of the test substance. The EU RAR reports the results of an acute dermal toxicity in the guinea pig which indicate that this species is more sensitive, however the results are not of relevance to classification. Sodium chromate is classified as (R21) 'Harmful in contact with skin' according to Directive 67/548/EEC and no change to this classification is proposed.

Sodium dichromate

Acute oral toxicity

The acute oral LD50 of sodium dichromate in the rat was found to be 123.5 mg/kg bw (males) and 86.5 mg/kg bw (females) in a proprietary, guideline-compliant study (Cuthbert & D'Arcy-Burt, 1983). Findings are consistent with those reported in the literature (EU RAR, 2005) and in an additional guideline-compliant study (Gad et al, 1986) which reported LD50 values of 56.64 and 39.02 mg/kg bw in males and females respectively. The UK IOH review (1997) also refers to a study by Gad et al (1986) which reported an acute oral LD50 value of 59 mg/kg bw, and may be the same as the proprietary study.

Sodium dichromate is listed on Annex I of Directive 67/548/EEC and is classified as (R25) 'Toxic if swallowed'. This classification is consistent with the results reported in the proprietary study and the published study and no change is proposed.

Acute inhalation toxicity

A proprietary study (Greenough & McDonald) reported 100% mortality for sodium dichromate at a concentration of 2.10 mg/l.

The results of an additional study (Gad et al, 1986) reported briefly in the UK IOH review (1997) reports an LC50 value of 200 mg/m3.

Sodium dichromate is listed on Annex I of Directive 67/548/EEC as (R26) 'Very toxic by inhalation'; this is consistent with the proprietary study and no change to this classification is proposed based on the results of this study and the results of a proprietary study performed with potassium dichromate (read-across).

Acute dermal toxicity

The acute dermal LD50 of sodium dichromate was found to be >2000 mg/kg bw in a guideline-compliant study (Cuthbert & D'Arcy-Burt, 1983). The findings of this study contrast with the results of an additional guideline-compliant study (Gad et al, 1986) using the same application conditions, in which a dermal LD50 of 960 mg/kg bw was determined for male rabbits. Signs of systemic toxicity were noted in a skin irritation study in the rabbit (Cuthbert & D'Arcy-Burt, 1982); the level of mortality in this study indicates a dermal LD50 of 250 mg/kg bw. Findings may be due to the use of a vehicle in this study which increased the bioavailability of the test substance. The EU RAR reports the results of an acute dermal toxicity in the guinea pig which indicate that this species is more sensitive, however the results are not of relevance to classification. Sodium dichromate is classified as (R21) 'Harmful in contact with skin' according to Directive 67/548/EEC and no change to this classification is proposed.

Potassium dichromate

Acute oral toxicity

The acute oral LD50 of potassium dichromate in the rat was found to be 168.0 mg/kg bw (males) and 90.5 mg/kg bw (females) in a proprietary, guideline-compliant study (Cuthbert & D'Arcy-Burt, 1983). Findings are consistent with those reported in the literature (EU RAR, 2005) and in an additional guideline-compliant study (Gad et al, 1986) which reported LD50 values of 74.11 and 47.94 mg/kg be in males and females respectively. The UK IOH review (1997) also refers to a study by Gad et al (1986) which reported an acute oral LD50 value of 74 mg/kg bw, and may be the same as the proprietary study.

Potassium dichromate is listed on Annex I of Directive 67/548/EEC and is classified as (R25) 'Toxic if swallowed'. This classification is therefore consistent with the available data and no changes are proposed.

Acute inhalation toxicity

A proprietary study (Greenough & McDonald) reported 100% mortality for potassium dichromate at a concentration of 1.72 mg/l. A guideline-comparable study (Hoffman, 1985) with potassium dichromate reported LC50 values of 99 and 83 mg/m3 in males and female rats respectively. The results of an additional study (Gad et al, 1986) reported briefly in the UK IOH review (1997) reports an LC50 value of 99 mg/m3. Potassium dichromate is classified as (R26) 'Very toxic by inhalation' according to Directive 67/548/EEC; this classification is consistent with the results of the Hoffman study and no change to this classification is proposed

Acute dermal toxicity

The acute dermal LD50 of potassium dichromate was found to be >2000 mg/kg bw in a guideline-compliant study (Cuthbert & D'Arcy-Burt, 1983). The findings of this study contrast with the results of an additional guideline-compliant study (Gad et al, 1986) using the same application conditions, in which a dermal LD50 of 1860 mg/kg bw was determined for male rabbit.

Potassium dichromate is classified as (R21) 'Harmful in contact with skin' according to Directive 67/548/EEC and no change to this classification is proposed.

Justification for classification or non-classification

Chromium trioxide

The literature studies indicate that chromium trioxide is classified according to EU criteria as (R25) 'Toxic if swallowed', (R24) 'Toxic in contact with skin' and (R26) 'Very toxic by inhalation'. This classification is consistent with the results of proprietary studies and the additional published information. No studies included in published reviews report lower LD50 values for chromium trioxide and no change to the classification is therefore proposed.

Sodium chromate

Sodium chromate is listed on Annex I of Directive 67/548/EEC and is classified as (R25) 'Toxic if swallowed', (R26) 'Very toxic by inhalation' and (R21) 'Harmful in contact with skin'. The proprietary studies report an acute oral LD50 of 67 -129.5 mg/kg bw and an acute dermal LD50 of >2000 mg/kg bw. An additonal study reported a lower dermal LD50 value of 1330 mg/kg bw. The acute inhlalation LC50 of sodium chromate is reported in a literature study to be 104 mg/m3; this value is also consistent with the acute inhalation LC50 of potassium dichromate in a proprietary study. The present classification is therefore consistent with the available data and no change is proposed.

Sodium dichromate

Sodium dichromate is listed on Annex I of Directive 67/548/EEC and is classified as (R25) 'Toxic if swallowed', (R26) 'Very toxic by inhalation' and (R21) 'Harmful in contact with skin'. The proprietray studies report an acute oral LD50 of 86.5 -123.5 mg/kg bw and an acute dermal LD50 of >2000 mg/kg bw. An additonal study reported a lower dermal LD50 value of 960 mg/kg bw

The acute inhlalation LC50 of sodium dichromate is reported in a literature study to be 200 mg/m3; this value is also consistent with the acute inhalation LC50 of potassium dichromate in a proprietary study.

The present classification is therefore consistent with the available data and no change is proposed.

Potassium dichromate

Potassium dichromate is listed on Annex I of Directive 67/548/EEC and is classified as (R25) 'Toxic if swallowed', (R26) 'Very toxic by inhalation' and (R21) 'Harmful in contact with skin'. The proprietary studies report an acute oral LD50 of 90.5 -168 mg/kg bw; and acute inhalation LC50 of 83 -99 mg/m3 and an acute dermal LD50 of >2000 mg/kg bw. An additional study reported a lower dermal LD50 value of 1860 mg/kg bw. The present classification is therefore consistent with the available data and no change is proposed.